Experimental Peritonitis Research Articles

Features of Microsurgical Anatomy of the Small Intestine in Experimental Widespread Purulent Peritonitis

The aim of experiment was to study the features of small intestine wall microanatomical constitution in widespread pyoperitonitis to justify the use of microsurgical intestinal suture. Material and methods . The proximal, middle and distal parts of the mesenterial intestine served as the research material. In animals with experimental peritonitis, a histotopographic method was used to perform serial transverse and longitudinal histotopograms with hematoxylin-eosin and picrofuchsine Van Gieson staining. The wall thickness of the intestine and its membranes was measured with an ocular micrometer through a stereoscopic microscope MBS-10. With the variational-statistical data processing, the mean value, the error of mean, the minimum and maximum values were determined. Results. Microscopic features in the wall of small intestine mesenterial part in dogs with widespread purulent peritonitis were described. Morphometric data on differences in the thickness of the intestinal wall and its membranes are presented. It was found that morphofunctional changes in the wall of the small intestine correlate with the period of peritonitis development. Conclusion. Based on the data obtained, it was concluded that microsurgical operation technique could be used during the reactive and toxic stages of widespread peritonitis.

PB2419 PEPTIDE CORRECTION OF OSMOTIC RESISTANCE DISORDERS IN INFLAMMATION

Background:The development of inflammation is accompanied by a change in the rheology of the blood ‐ an increase in viscosity, aggregation, a decrease in the osmotic resistance of red blood cells, which indicates a change in the structure of their membrane. This leads to a change in the functional properties of red blood cells and impaired microcirculation. The search for new anti‐inflammatory drugs, devoid of side effects is relevant. Promising may be endogenous regulatory peptides of the glyproline family, which have a prophylactic and therapeutic effect in various pathological conditions.Aims:The aim of this study was to investigate changes in the osmotic resistance of erythrocytes in the dynamics of experimental peritonitis with the introduction of the peptide Pro‐Gly‐Pro (PGP).Methods:A pro‐inflammatory agent was used to simulate experimental peritonitis ‐ 40% sodium thioglyaolate solution 4 g/kg, administered intraperitoneally. The erythrocyte osmotic resistance (ORE) was determined 30 minutes, 2 and 18 hours after the induction of inflammation. The evaluation of the wholesale electricity market was carried out to determine the degree of hemolysis in hypotonic solutions of sodium chloride. The light transmittance was recorded on a photoelectrocalorimeter at a wavelength of 580 nm. All experiments were performed in accordance with the ethical principles and regulatory documents recommended by the ESF and the declaration of a humane attitude towards animals.Results:The development of inflammation is accompanied by a decrease in the osmotic resistance of erythrocytes. Statistically significant differences in the wholesale electricity market from control were observed 2 hours after the administration of the thioglycolate. The introduction of PGP peptide at a dose of 3.7 μm/kg before the induction of inflammation reduced pathological changes in the ORE. The percentage of hemolyzed cells decreased, the differences were significant in solutions with salt content of 0.4% and 0.3%. The peptide, introduced against the background of developed inflammation (1 hour and 45 minutes after the introduction of thioglycolate) did not have a corrective effect on the ORE.Summary/Conclusion:The results indicate the ability of PGP to exert a preventive protective effect on the erythrocyte membrane, preventing a decrease in the ORE.

Роль модификаций липидов тканей печени в патогенезе хирургического эндотоксикоза

Цель. Оценка роли модификаций липидов тканей печени в ее детоксикационной способности при остром перитоните. Методика. В эксперименте у собак моделировали острый перитонит различной степени тяжести. Степень эндогенной интоксикации оценивали по уровню токсических продуктов гидрофильной и гидрофобной природы. Представлен новый способ оценки детоксикационной функции печени на основе определения уровня токсических продуктов в крови, притекающей к органу и оттекающей от него. Для характеристики качественного и количественного состава липидов из биопсийного материала печени выделяли липиды, осуществляли их фракционирование и денситометрию. Оценивали интенсивность перекисного окисления липидов, активность фосфолипазы А2 и супероксиддисмутазы. Результаты. Показано, что функциональное состояние печени при хирургическом эндотоксикозе коррелирует с модификацией липидов ее тканевых структур, проявлением чего были существенные изменения состава основных липидов и резкое увеличение хаотропных фракций. Установлена сопряженность изменений состава липидов тканей печени со степенью тяжести патологического процесса. Одними из значимых триггерных механизмов липиддестабилизирующих явлений в тканевых структурах печени являются оксидативный стресс и высокая фосфолипазная активность. При тяжелом течении острого перитонита высока вероятность такого нарушения функционально-метаболического состояния печени, при котором она приобретает самостоятельное патогенетическое значение в продукции токсических субстанций. Заключение. В патогенезе синдрома эндогенной интоксикации при остром перитоните важную патофизиологическую значимость имеет модификация липидов тканей печени, которая является основой острой печеночной недостаточности и формирования нового состояния органа - источника токсинов. Полученные данные определяют векторы патогенетической терапии по предупреждению необратимых повреждений печени с высоким риском неблагоприятного исхода. Background. Despite the interest to the issue of surgical endogenous intoxication, mechanisms of impaired hepatic detoxification function in endogenous intoxication induced by acute peritonitis are studied insufficiently. Aim. To elucidate the role of modifications in membrane lipids of liver cells in imparing its detoxification ability in acute peritonitis. Methods. Acute peritonitis of different severity was modeled in dogs. The authors presented a new method for evaluating the liver detoxification function based on measuring concentrations of toxic products in the blood inflowing to and outflowing from the liver. Hepatic lipids were separated, fractionated and studied by densitometry. The qualitative and quantitative composition of liver lipids, intensity of lipid peroxidation, and activities of phospholipase A2 and superoxide dismutase were measured in liver tissue in the dynamics of experimental peritonitis. Results. In surgical endogenous intoxication, the liver function correlated with the modifications of tissue lipids evident as considerable changes in the composition of major membrane-forming lipids and an increase in chaotropic fractions (fatty acids, lysophospholipids). Changes in the tissue lipid composition correlated with severity of the pathological process. Significant triggering mechanisms for the hepatic lipid modification were oxidative stress and a high phospholipase activity. Conclusion. In severe acute peritonitis, there is a high probability of profound functional and metabolic disorders in the liver so that it acquires an independent pathogenetic significance as a producent of toxic substances.

STATUS OF THE HUMORAL LINK OF IMMUNITY AT EXPERIMENTAL PERITONITIS ON THE BACKGROUND OF DIABETES MELLITUS

Introduction. The combined course of acute peritonitis and diabetes increasingly leads to the development of secondary immunodeficiencies, which contribute to an increase in the percentage of postoperative complications and fatalities, the emergence of complexity of treatment and diagnosis.
 The aim of the study – to learn the peculiarities of humoral link of the immune response in the organism of experimental animals during simulated acute common peritonitis on the background of diabetes mellitus compared with animals with experimental acute peritonitis alone.
 Reserch Methods. 56 white rats were used in this work. Diabetes mellitus was modeled by intraperitoneal administration of Srethosotocin from “Sigma” firm with the rate of 7 mg per 100 g of animal mass, acute peritonitis – insertion of 0.5 ml of 10 % of the captured fecal suspension into the abdominal cavity of the animals. The concentration of immunoglobulins in serum was determined. Observation time points: 1, 3, and 7 days from the beginning of the peritonitis modeling.
 Results and Discussion. Analyzing the results of studies, it can be stated that there were observed directed changes in the concentration of immunoglobulins in blood serum of rats of different groups. Thus, on the first day after simulating acute common peritonitis on the background of diabetes, the level of Ig G decreased by 1.5 times, Ig M – by 1.3 times and Ig A – by 1.4 times (p<0.05). On the seventh day of the experiment, levels of all classes of immunoglobulins were statistically significantly lower than those of the group with acute common peritonitis: Ig G level was lower by 21 %, Ig M and Ig A were lower by 17 % and 56 % respectively (p<0.05). The results of our studies indicate that the presence of diabetes in acute general peritonitis leads to a decrease in the resistance of the humoral level of the immune system with antigenic stimulation and secondary immunodeficiency states.
 Conclusion. In animals with acute peritonitis, protective mechanisms of the humoral immunity level are substantially reduced on the background of diabetes, which is confirmed by statistically significantly lower levels of immunoglobulins of classes A, M, G compared to a group of animals with a pattern of acute peritonitis. The revealed functional impairment of humoral immunity indicates an appreciable weakening of the organism's protection factors in acute peritonitis on the background of diabetes mellitus with the development of secondary immunodeficiency.

Influence of intraabdominal hypertension on morphological changes of internal organs in experiment

The development of intra-abdominal hypertension is possible with a wide range of surgical pathologies, in particular, the abdominal cavity, as well as in other nosologies and significantly aggravates the prognosis. Thus, polytrauma and major burns present up to 60% of the risk of abdominal compartment syndrome (AKS), and intestinal obstruction, peritonitis and acute destructive pancreatitis - in almost 80% of cases. The purpose of the work was to investigate the morphological changes that occur in the internal organs in an intraabdominal hypertension syndrome caused by peritonitis. The experiment was conducted on 28 guinea pigs, divided into three groups: I — the control group (n=8), the II group, in which the peritonitis was simulated by destruction of the colon in the experimental animals (n=10), III — the group of experimental animals, in which the peritonitis model was combined with a paranephrine blockade in combination with a blockage of the circular ligament of the liver (n=10). In all experimental animals, intraabdominal pressure was measured every 6 hours during the day. The results were processed using Microsoft Excel spreadsheet formulas using the Student t criterion. For morphological study section material was used (fragments of the kidneys, small intestine and peritoneum). To facilitate cutting the pieces, we carried out preliminary fixation of organs in 10% neutral formalin (at least 24 hours). From each organ, cut into 1–2 bits or ribbons, which were fixed in 10% neutral formalin solution. After posting according to the generally accepted method, bits were poured into paraffin. Paraffin sections 5–7 microns thick were stained with hematoxylin and eosin. As a result of experimental work, it has been found that combined regional blockades effectively reduce intra-abdominal pressure within six hours after use, but their effect is short-lived. In the experimental peritonitis group, with the implementation of regional blockades with lidocaine solution, the morphological changes of the kidneys and peritoneum were less pronounced. Improvement of the technique of regional blockades, in particular the continued infusion of local anesthetics, can significantly increase the effectiveness of the technique without side effects that are inherent in, in particular, peridural analgesia.

Tanshinone IIA attenuates sepsis-induced immunosuppression and improves survival rate in a mice peritonitis model

BackgroundThe importance of sepsis-induced immunosuppression and its contribution to mortality has recently emerged. In this study we examined the effects of Tanshinone II-A (TSN), a widely used traditional Chinese medicine, on immunosuppression in experimental peritonitis induced septic mice. Materials and methodsSepsis was achieved by means of cecal ligation and puncture (CLP). TSN at different doses (5, 15 and 45 mg/kg, i.p.) were used at different time-points (0, 3, 6 and 12 h) after CLP to evaluate its effect on the survival of septic mice. In parallel experiments, mice given TSN at optimal dose and time-point were euthanized to collect peritoneal macrophages, blood and tissue samples at 24 h after the CLP. ResultsTSN improved the survival of septic mice in a dose- and time-dependent manner. TSN reduced CLP-induced serum biochemical parameters and protected organs from histopathological injuries. CLP-induced apoptosis and decreased percentages of splenic CD4+ and CD8+ T cells were reversed in TSN-treated mice. Moreover, CLP-induced formation of regulatory T cells (Treg) in the spleen was abolished in TSN-treated mice. CLP greatly decreased the levels of interferon-γ and interleukin (IL)-2 in the spleen, while the levels of IL-4 and IL-10 increased after CLP. TSN completely reversed these alterations and elicited a more-balanced Th1/Th2 response. Moreover, TSN promoted macrophage phagocytotic activity and improved bacterial clearance of septic mice. Lastly, TSN abolished CLP-triggered increase in serum HMBG1 level. And HMGB1 neutralization could increase the percentages of splenic CD3+CD4+/CD3+CD8+ lymphocytes and decreased the Treg population. ConclusionsOverall, our data suggest that TSN exerts immune modulatory effect and might be a useful strategy to ameliorate immunosuppression in polymicrobial sepsis.

Sepsis Induced by Cecal Ligation and Puncture.

Despite advances in intensive care unit interventions, including the use of specific antibiotics and anti-inflammation treatment, sepsis with concomitant multiple organ failure is the most common cause of death in many acute care units. In order to understand the mechanisms of clinical sepsis and develop effective therapeutic modalities, there is a need to use effective experimental models that faithfully replicate what occurs in patients with sepsis. Several models are commonly used to study sepsis, including intravenous endotoxin challenge, injection of live organisms into the peritoneal cavity, establishing abscesses in the extremities, and the induction of experimental polymicrobial peritonitis via cecal ligation and puncture (CLP). Here, we describe the surgical procedure of CLP in mice, which has been demonstrated to closely replicate the nature and course of clinical sepsis in human subjects.

STRUCTURAL CHANGES OF THE COLON WALL IN CASE OF DEVELOPMENT OF ENTERAL INSUFFICIENCY CAUSED BY EXPERIMENTAL PERITONITIS

Objective: to study structural changes of the colon wall and development of enteral dysfunction in an experimental course of acute peritonitis. Materials and Methods. Experimental studies were conducted on 21 mature albino nonlinear rats. Under thiopental anaesthesia peritonitis was caused by puncture of the ascending colon and the introduction of freshly prepared 15% solution in the dose of 0.5 ml per 100 g of the body weight of a rat. On the 1st, 3rd and 7th day of experimental peritonitis animals were decapitated under calypsol anesthesia. The pieces of the small intestine were taken for histological examination determining changes histologically. Results. Structural changes were found to occur on the first, third, and 7 day of experimental peritonitis in the lining of the colon and continued to grow over time, manifested by its consolidation at the expense of pronounced lymph and histiocytic infiltration and combined focal leukocyte infiltration, corresponding to morphological structure of colitis. Lumen of crypts is reduced at the expense of an increased activity of secretory epithelial cells and degenerative changes. Uneven blood supply of the vessels combined with perivascular edema is found in the subepithelial layer. Conclusion. Increased secretory activity and development of degenerative changes in the superficial epithelium occur in the colon mucosa during experimental peritonitis. Epithelial degenerative changes with pronounced histiocytic and lymph infiltration of the stroma and its edema increase from 3 to 7 days.

Combined Effect of Silver Nanoparticles, Ceftriaxone, and Methyluracil during Experimental Purulent Peritonitis.

Bacterial biofilms provoke and/or promote the most chronic and recurrent infectious diseases. Previously, experimental models of purulent peritonitis and meningoencephalitis revealed positive antibiofilm effect of metallic nanoparticles and the absence of resistance against such nanoparticles in microorganisms. This study examines the combined effect of silver nanoparticles with ceftriaxone and methyluracil on recovery mechanisms during inflammatory diseases exemplified by purulent peritonitis in experimental animals.

Investigation of hematological indices in experimental peritonitis

Objective. To investigate hematological indices on the first, third and seventh day of the experimental peritonitis development.
 Маterials and methods. The investigation was conducted on 180 Wistar line rats with a body mass 180 - 200 g. The animals were divided into four Groups: Group I - 20 intact animals; Group II - 80 animals, in whom a biliary peritonitis was simulated without further correction; Group III - 40 animals, in whom the biliary peritonitis simulated was corrected, using abdominal cavity sanation with chlorhexidine solution and further application of standard antibioticotherapy; Group IV - 40 animals, in whom a simulated biliary peritonitis was corrected in accordance to combined scheme of detoxication.
 Results. While investigation of hematological markers in animals of Group IV, to whom complex treatment was applied, a positive dynamics of indices of the erythrocytes quantity, hemoglobin concentration, hematocrit and ERS were observed on the third day and preserved up to the seventh day. The indices of the leucocytes quantity more significantly had normalized on the first and third days. The leucocytic index of intoxication had lowered on the third day. Most pronounced positive dynamics of the AST activity was observed on the seventh day, and of the ALT - on the third. On the first and third day of experiment the least pronounced lowering of the general protein concentration was noted, and on the seventh day - its raise. Concentration of general bilirubin maximally approached the indices of intact animals on the third day.
 Conclusion. Investigation of hematological markers have proved the efficacy of our proposed method of the abdominal cavity sanation.

The antibacterial effect of peritoneal fluid in experimental peritonitis.

In our study, the effects of peritoneal fluid on some Gram-negative and Candida albicans in experimental peritonitis rats were studied. The primary objective of the present study was to understand the effect of peritoneal fluid on microorganisms causing intra-abdominal infections. Twenty male Sprague-Dawley rats weighing between 250 and 300 g were used in the study. The rats were randomly divided into two groups consisting of 10 animals. The operative procedures were performed under sterile conditions. In group I, sham laparotomy was done. In group II, the distal part of the cecum was ligated, and cecum perforation was performed. Peritoneal fluid samples at baseline and 2 and 4 h were extracted using a Pasteur pipette during laparotomy under anesthesia. Peritoneal fluid was ineffective on Citrobacter freundii, Proteus mirabilis, and Enterobacter aerogenes. It inhibited the growth of Klebsiella pneumoniae for 8 h. However, growth was significantly increased in the passages obtained after 24 h. The growth of C. albicans decreased in the passages that were extracted after 4 and 8 h and increased in the passages obtained after 24 h (p<0.05). It was found that the number of Escherichia coli and Pseudomonas aeruginosa colonies that were grown in 2 h decreased, and no growth was detected in the passages obtained after 2 h (p<0.05). Proliferating colony counts of E. coli and P. aeruginosa decreased after 2 h, and there was no proliferation in subsequent cultures. Peritoneal fluid exhibits a bactericidal effect under appropriate conditions. It also exhibits peritoneal bactericidal activity against E. coli, the major pathogen in intra-abdominal infections.

Synthetic mesh placement in the presence of abdominal infection: An experimental study of feasibility.

There are varying opinions on the feasibility of the placement of synthetic materials in contaminated surgical fields. The aim of this study was to investigate the outcomes of the use of a commercially available composite mesh in the presence of abdominal infection. Twenty-four hours after the induction of experimental peritonitis, 20 rats were randomized into 2 groups of 10 subjects. After abdominal cleansing with a second laparotomy, the abdomen was closed with running sutures in the control group and the composite mesh was applied in the experimental group before closure. The rats were followed up for findings of sepsis, mortality, and wound infection. On the 28th day, the rats were sacrificed and evaluated for abdominal infection, abdominal adhesions, and bacterial growth in the mesh and tissue cultures. The mortality rate was 0% and 30% in the control and mesh groups, respectively (p=0.21), and the wound infection rate was 20% and 57.1% (p=0.162). In the mesh group, the adhesions were significantly more intense (p=0.018) and significantly more microorganisms proliferated in the tissue cultures (p=0.003). The significant increase in the intensity of adhesions and bacterial proliferation, as well as the higher rate of mortality and wound infection in the mesh group indicated that this composite mesh cannot be used safely in the repair of abdominal defects in the presence of abdominal infection.

The role of bacteriophages in the complex treatment of peritonitis of appendicular origin (experimental study)

Relevance: with the management of laparoscopic methods of surgical treatment of acute appendicitis, the problem of the occurrence of early postoperative complications has not changed at present, which makes it necessary to carry out preventive measures.&#x0D; Objective: to study the possibility of improving the results of surgical treatment of peritonitis, the most frequent complication of acute appendicitis, by reducing the number of postoperative complications of infectious genesis.&#x0D; Methods: Studies were performed on 47 non-linear white rats weighing 200-250 grams by modelling peritonitis using the biological model as an example, followed by antibiotic therapy and combination therapy using bacteriophages. To model peritonitis, the infection of the abdominal cavity with the E. coli strain 25922 was used. The laboratory animals were divided into 3 groups: the first group was control group, the second group received treatment in the form of a single intraperitoneal injection of Cefipime, the third group received treatment as a single intraperitoneal injection of the Sextapage.&#x0D; Results: the evaluation of the methods was carried out on the basis of the study of the clinical picture of the course of peritonitis in experimental animals, the data of pathomorphological and histological examination of the sectional peritoneum. As a result of experimental studies, there was no significant difference in the methods of perioperative prevention of complications of acute appendicitis, which makes it possible to perform monotherapy with bacteriophages. Phages in comparison with antibiotics have no less therapeutic efficacy.&#x0D; Conclusions: Thus, our experimental studies revealed completely satisfactory results of monotherapy of experimental peritonitis with a bacteriophage. According to the morphological data, the inflammatory process in the abdominal cavity is stopped by the phage fast enough and there is a tendency for a faster fading of the inflammation than in the treatment with antibiotics.

CHARACTERISTIC FEATURES OF MULTIPLE ORGAN FAILURE IN CASES OF PERITONEAL SEPSIS

Background. The study of hystomorphology of liver and small intestine in experimental peritonitis is presented. Due to this information the criterion of pathogenetic moment transition SIRS for peritoneal sepsis was determined.Objective. The aim of the research was to study the morphology of terminal part of small intestine and liver in cases of experimental peritonitis.Methods. For histological and electron microscope study the biopsy of liver, small intestine were taken; the samples were stabilized in a neutral formalin, dried in alcohol of increasing concentration and placed in paraffin. Paraffin sections were painted with hematoxylin and eosin and studied under the light-optical microscope.Results. Apoptosis caused damage to enterocytes and hepatocytes of first bacterial translocation. Mechanism of vasodilatation effect of NO and its effect on apoptosis were determined. Septic shock was accompaniment of two main levels of body cells damage: apoptosis and membranes destruction. Peritoneal sepsis is a grave condition caused by progressive peritonitis and polyorgan insufficiency syndrome. The phases of peritonealis sepsis pathogenesis were defined.Conclusions. The presented morphological criteria prove the initiation of apoptosis within 24 hours after the development of peritonitis in enterocytes and hepatocytes.

СТРУКТУРНО-ФУНКЦІОНАЛЬНА РЕАКЦІЯ ЛЕГЕНЕВОЇ ТКАНИНИ ТА СУДИН МАЛОГО КОЛА КРОВООБІГУ ЛАБОРАТОРНИХ ЩУРІВ НА РАННІЙ СТАДІЇ МОДЕЛЮВАННЯ ГОСТРОГО ПЕРИТОНІТУ

Метою нашого дослідження було експериментальне вивчення морфофункціональних змін в легеневій тканині при розвитку гострого перитоніту.Матеріал і методи дослідження: морфометричний (вимірювання товщини міжальвеолярних перегородок, діаметра альвеол); гістологічний з метою вивчення структури легеневої тканини на світлооптичному рівні, статистичний. Експерименти виконано на 40 білих щурах-самцях, 10 тварин складали інтактну контрольну групу, 30 тваринам моделювали гострий перитоніт.Результати досліджень. Незважаючи на істотний прогрес клінічної медицини, перитоніт і пов’язані з ним ускладнення залишаються однією з важливих проблем хірургічної практики. Поліорганна недостатність як наслідок гострого перитоніту є вагомою причиною ускладнення захворювання і летальності, при цьому одним з перших органів-мішеней є легені. У дослідженні вже під час розвитку токсичної стадії гострого перитоніту спостерігали морфологічні ознаки реакцій кровоносних судин як в легенях, так і в бронхах на світлооптичному рівні. У просвітах бронхіол спостерігали злущені епітеліоцити. Реакцією на перебіг патологічного процесу стала активація секреторної функції келихоподібними клітинами слизової бронхів, локальне розширення альвеол, потовщення більшості альвеолярних перегородок. Характерна поява у цей час спазмованих бронхіол.Висновки. Експериментальний гострий перитоніт у білих щурів-самців спричинив реакцію як на рівні епітелію бронхів, альвеол, так і в судинній ланці. Ендотоксикоз, спричинений гострим перитонітом, викликав розвиток дистрофічних процесів і порушення нормальних тканинно-судинних взаємовідносин. Протягом ранньої стадії гострого перитоніту перебіг компенсаторно-пристосувальних реакцій відбувався паралельно з розвитком ознак деструкції: спостерігали підвищення секреторної активності келихоподібних клітин, збільшення просвіту окремих альвеол, потовщення міжальвеолярних перегородок, набряки структурних елементів стінок судин.

Динамика показателей белой крови в условиях экспериментального желчного перитонита

Динамика показателей белой крови в условиях экспериментального желчного перитонита

The state of free-radical oxidation and antioxidant system at the experimental acute peritonitis associated with hypothyroidism

To study the influence of hypothyroidism on the course of free-radical processes and state of antioxidant system in rats with acute extensive peritonitis, the production of active forms of oxygen by mononuclear leukocytes, concentration of lipid hydroperoxides, TBA-active products, Schiff bases, SOD and catalase activity were determined. Simulation of extensive peritonitis with associated hypothyroidism led to the less obvious, than in euthyroid rats, increase of active forms of oxygen and lipid peroxidation products. Although the reduction of activity of enzymes of the first line of antioxidant defense (superoxide dismutase and catalase) was more evident.

Comparative efficacies of daptomycin, vancomycin, and linezolid in experimental enterococcal peritonitis.

Enterococci have become increasingly important pathogens for nosocomial infection (e.g. bacteremia, intra-abdominal infection, endocarditis, etc.), related to their intrinsic resistance to many antibiotics. Although the invitro susceptibility of daptomycin (DAP) against Enterococci is well established, the Food and Drug Administration has only approved its use for complicated skin and skin structure infections induced by Enterococcus faecalis. In this study we evaluated the potential therapeutic application of DAP in a murine model of enterococcal experimental peritonitis. Mice were injected intraperitoneally with 4×1010 colony-forming units of Enterococcus faecium. DAP alone, DAP combined with ampicillin, vancomycin, or linezolid were administered 2h after enterococcal inoculation and examined the survival, viable bacteria counts, the level of KC/CXCL1 in the peritoneal fluid. The viable bacteria counts in the peritoneal fluid of the DAP- or DAP plus ampicillin-treated groups were decreased significantly compared to those of the vancomycin- and linezolid-treated groups (P<0.05) at 6 and 12h after the inoculation of Enterococcus. The level of neutrophil chemoattractants KC in the peritoneal fluid at 12h after enterococcal inoculation was significantly decreased in the DAP plus ampicillin-treated group (P<0.05). In addition DAP showed the inhibitory effect of enterococcal biofilm formation dose-dependently by a microtiter biofilm assay. These results indicate that DAP, particularly with β-lactams, is a possible alternative agent to treat severe enterococcal infection such as peritonitis.

Establishment of Experimental Murine Peritonitis Model with Hog Gastric Mucin for Carbapenem-Resistant Gram-Negative Bacteria.

Animal models are essential to studies of infectious diseases. The use of mice to test bacterial infection has been extensively reported. However, methods applied to clinical isolates, particularly for carbapenem-resistant bacteria, must be tailored according to the infection models and bacteria used. In this study, we infected 6-week-old female BALB/c mice intraperitoneally with different strains of resistant bacteria plus 3% hog gastric mucin. This method was found to be efficient and readily applicable for investigation of carbapenem-resisant Gram-negative pathogens (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) detected in Korea.

Innate Immunity of Adipose Tissue in Rodent Models of Local and SystemicStaphylococcus aureusInfection

Background. The role of adipose tissue in systemic inflammation during bacterial infection is unclear. Effects of Staphylococcus aureus infection on adipocytes in rodent models of experimental endocarditis and peritonitis, the impact of S. aureus infection on gene expression in epididymal and subcutaneous adipose tissue, and effects of S. aureus infection on the toll-like receptor-2- (TLR2-) cathelicidin pathway in vivo and in vitro were investigated. Material and methods. The rat model of catheter-induced S. aureus endocarditis and the mouse model of S. aureus-induced peritonitis were used for infection experiments, gene expression profiling in adipose tissue, and measurement of cytokines. 3T3-L1 adipocytes were analyzed for expression of the TLR2-cathelicidin pathway. Results. Upon systemic bacterial infection by S. aureus, there is a shift from anti- to proinflammatory cytokines in serum and in adipose tissue gene expression. The TLR2-cathelicidin pathway is increasingly expressed during adipocyte differentiation in vitro and is induced upon stimulation by synthetic lipopeptides. Conclusions. Systemic infection by Gram-positive bacteria induces proinflammatory transformation of adipose tissue sites distinct from infection sites, documented on the levels of gene expression and secreted mediators. The TLR2-cathelicidine pathway is expressed and highly inducible in adipocytes in vitro. Lipopeptides are important immune-modulators of adipocytes in both gene expression and protein secretion.