Role of cytokines in the pathogenesis of diffuse bacterial peritonitis

We analyzed present-day data in Russian and foreign literature on development of cytokine cascade in diffuse bacterial peritonitis having studied the role of cytokines in forming systemic inflammation response syndrome. It has been showed that cytokines primary regulate local protective response by forming typical inflammatory reaction with its classic local manifestations and natural anti-microbial resistance mechanisms. The main stage in the development of diffuse bacterial peritonitis is a disbalance in the system of proinflammatory cytokines and anti-inflammatory mediators; and this disbalance defines the severity of extraabdominal complications and multisystem organ failure. In the article, the markers of inflammation severity are described assisting in evaluation of the course of inflammation process and postoperative survival rate. Due to changes in immune system of the patients, it is necessary to assess complexly their immune status including cytokine profile, which in this group of patients is of diagnostic and prognostic value and needs to be further studie

Modern features of VATS treatment of spontaneous pneumothorax as a complication of bullous lung emphysema: a systematic literature review

The article presents a literature review on the VATS treatment of spontaneous pneumothorax as a complication of bullous lung emphysema. The review considers questions of etiology, diagnostics and therapeutic tactics in VATS treatment of spontaneous pneumothorax with bullous emphysema. The main target of surgeons is not only elimination of spontaneous pneumothorax, but quick exposure of lung parenchyma pathology in order to predict possible reoccurrence of spontaneous pneumothorax. Video-assisted thoracoscopy in this case is a mini-invasive, less traumatic and highly efficient method of treatment of spontaneous pneumothorax. Anti-relapsing surgical interventions with pleurodesis are unanimously considered to be necessary. An integrated and differentiated approach to the treatment of spontaneous pneumothorax as a result of bullous emphysema helps to determine diagnostic and therapeutic tactics of VATS treatment and choice of pleurodesis induction leading to improved treatment outcomes in this category of patients

Adhesive Process of the Abdominal Cavity as a Risk Factor for the Development of Postoperative Intestinal Fistula

Adhesive disease of the abdominal cavity remains one of the unresolved problems of abdominal surgery. The clinical picture of the pathological process is diverse, treatment of patients is not always effective, and decision-making on the use of certain medical methods is often difficult.The aim of the research was to assess the severity of the adhesive process and the likelihood of complications in patients with adhesive disease of the abdominal cavity.Materials and methods. We performed the retrospective analysis of 160 case histories of patients for the period 2006-2010, who, according to emergency indications, were admitted to the surgical department of the Irkutsk Regional Clinical Hospital with a clinic of acute adhesive intestinal obstruction against the background of adhesive disease. To assess the severity of the adhesive process, our own scale for assessing the adhesive process of the abdominal cavity was developed and tested in clinical conditions. To assess the likelihood of developing postoperative unformed intestinal fistulas, a prospective analysis of the treatment of 36 patients with acute adhesive intestinal obstruction was performed.Results. The severity of the adhesive process in the operated patients was 13 (10-15) points, which indicates a pronounced adhesive process. In patients operated repeatedly for commissural intestinal obstruction, the severity of the adhesion process according to the proposed scale was 14 (14-15) points, which corresponds to pronounced adhesion of the abdominal organs. Based on the proposed scale, the probability of developing postoperative unformed intestinal fistulas was calculated. The sensitivity and accuracy of the probability scale was 71 % (CONSORT). Thus, an intraoperative assessment of the severity of the adhesive process allows us to predict the likelihood of postoperative external intestinal fistula

Experimental Modeling of General Purulent Peritonitis

General purulent peritonitis takes one of the first places in the structure of purulent complications. Despite the im provement of methods of diagnosis and treatment, mortality in postoperative purulent peritonitis remains quite high.Aim of the study: develop a reproducible model of postoperative general peritonitis to study the pathophysiological mechanisms of its development and the development of pathogenetically substantiated therapy.Materials and methods. The study was performed on 18 Wistar male rats aged 6 months, weighing 250–300 grams. Animals underwent laparotomy and modeling of postoperative general peritonitis according to the proposed method. Hospital strains of Escherichia coli BRLS 109 and Bacteroides fragilis 109 (strain ISCST1982, registered in Genbank), which we isolated from patients with acute appendicitis, with a total volume of 1.0 ml per animal, were used as infectious agents. Animals were taken out of the experiment under anesthesia with compliance with the rules of euthanasia at 1st, 3rd, 7th days after surgery. For morphological studies, samples of a fragment of the abdominal wall and cecum were taken. Bacteriological studies were performed on the 3rd, 7th day from the beginning of the experiment.Results. It was established that all animals developed peritonitis with the progression of purulent-destructive changes in the abdominal cavity and the development of adhesions, which was confirmed by the data of the morphological method of research. According to the results of bacteriological studies on the 3rd day, exudate infection was detected in all rats (in 100 % of observations). E. coli BLS were isolated in all cases at concentrations of 103–104 CFU/ml. The strain B. fragilis is inoculated in 3 animals at a concentration of 103 CFU/ml, which made 50 %. By the 7th day, only an aerobic E. coli strain of BLS was detected in peritoneal exudate at concentrations of 103 CFU/ml in the complete absence of growth of B. fragilis.Conclusion. We have developed a model of postoperative general peritonitis, which allows us to study the dynamics of the development of the inflammatory process in the abdominal cavity and, in terms of its clinical manifestations, is close to a real human disease. The reproducibility of the model is 100 %, which is confirmed by microbiological and morphological data

Involvement of the ERK MAPK Cascade in the Formation of Adhesions in the Abdominal Cavity

Background. ERK1 and ERK2 (extracellular signal-regulated kinase) are related protein serine / threonine kinases that are involved in the regulation of the cell cycle, cell migration and survival, differentiation, metabolism, and proliferation. Evaluation of this cascade is promising to determine the possibility of influencing  pathological conditions through the regulation of ERK1/2.Aim of the study. To assess the involvement of the ERK MAPK cascade in the development of adhesions in the abdominal cavity.Methods. The experiments were carried out on male Wistar rats. The adhesion process in the abdominal cavity was simulated (n = 40). The research time is from 2 hours to 30 days. Tissue samples from 5 intact animals were examined as a control. Histological sections were prepared and stained histochemically for ERK1. The expression of ERK1 and ERK2 was assessed by PCR.Results. Using the PCR method, the involvement of both the ERK1 and ERK2 cascades in the process was established, and, judging by the change in gene expression, the latter is more actively involved in the process. Histochemical study confirmed the role of ERK cascades in the management of repair in serous membrane injury. Histochemically revealed an increase in ERK1 expression with two peaks of activity – at 1 and 30 days.Conclusion. Our data establish multichannel control of the reparative process in the area of damage to the serous membrane with the involvement of both the p38 and ERK MAPK cascades, which is important to consider when developing methods of influencing the wound healing process in the abdominal cavity

An examination of hepatotoxicity and nephrotoxicity of a new antiadhesive preparation (experimental study)

Adhesive process in the abdominal cavity was simulated in Wistar rats. The animals were divided into two groups: the main one - simulation of adhesive process in the abdominal cavity and introduction of 3 ml of saline into the abdominal cavity; and the controls - simulation of adhesive process in the abdominal cavity and introduction of 3 ml of new antiadhesive preparation. We evaluated biochemical parameters at eight time points during the period from 2 hours to 28 days. The introduced drug for adhesion prevention did not affect the protein-synthetic function of the liver: the blood level of whole protein was the same in both groups and remained within the normal range throughout the follow-up period. The blood level of creatinine, which is the end product of protein metabolism reflecting the renal excretory function, was within normal values in both groups throughout the observation period. Significant differences between the groups were noted only on the 28th day of the experiment: in the main group creatinine level was higher as compared to the control group (p = 0.014), but remained within the normal range. The same pattern was observed when evaluating the blood urea level, which reflects the renal excretory function - the blood urea level remained normal in both groups throughout the experiment. Hence, the new antiadhesive drug does not produce toxic effect on liver and kidneys in a single intraperitoneal introduction in experiment. Biochemical indices are the same as in single intraperitoneal infusion of saline

EXPRESSION OF COLLAGENS IN THE DAMAGE AREA AT ABDOMINAL ADHESIONS

Background. Postoperative adhesions are a serious problem in surgery. However, at the present time molecular mechanisms of the adhesion process are insufficiently studied. Aim. To study the dynamics of expression of genes encoding the synthesis of collagen in case of damage to the serosa on the example of the peritoneum in conditions of aseptic inflammation. Materials and methods. Aseptic inflammatory process in the abdominal cavity was modeled (Wistar rats, n = 40). A micro- and macroscopic picture of the damage area was studied. Immunofluorescent staining for Type I collagen (Col 1A1) was performed. The expression of genes encoding collagen of different types was evaluated using the RT2-Profiler PCR kit Array Rat Wound Healing. Results. It has been established that the adhesion process with peritoneal damage in aseptic conditions reaches its maximum by the 30th day of observation. The same period coincides with the maximum of collagen synthesis in fibroblasts in the repair area, revealed by immunofluorescence study. The interrelation of synthesis of type I and III collagens went as expected - the onset of expression of type III collagen (from day 3) is ahead of the expression of collagen type I (from day 7). Peak gene expression of collagens type I, Alpha-1 and -2; type III Alpha-1, type IV Alpha-1 and -3, type V Alpha-1, -2 and -3; type XIV Alpha-1 (Col14a1) falls on the 14th day. For the first time, active involvement of type V alpha-3 collagen in the adhesion process was noted - we detected both early (from day 1) and maximum intensive (up to 166.96 times increase in comparison with intact animals). Conclusion. Perhaps, the hyperexpression of collagen V alpha-3 that we revealed is an important link in the pathogenesis of adhesion in the abdominal cavity

Study of the effect of a new antiadhesive agent on peripheral blood indices (experimental study)

Adhesive process in the abdominal cavity was simulated in Wistar rats, which were divided into two groups: the main one - simulation of adhesive process in the abdominal cavity and introduction of 3 ml of saline into the abdominal cavity; the controls - simulation of adhesive process in the abdominal cavity and introduction of 3 ml of new antiadhesive preparation. The mechanism of drug action bases on the ability to inhibit the growth of connective tissue in the adhesion area by effecting the activity of mitogen-activated protein kinases. Examination of peripheral blood indices was performed at eight time points during the period from 2 hours to 28 days. The concentration of red blood cells in the peripheral blood in both main and control groups decreased moderately in the early postoperative period (2 hours, 6 hours and 12 hours), and this rate was significantly lower in the control group as compared to the main one by 12 hours term. Later the index restored to normal. Hemoglobin concentration in the peripheral blood was higher in the main group than in the control one, the differences were significant in 2 hours, 3 days, 28 days. The level of hematocrit in the main group was higher than that in the controls during the entire follow-up period; the difference was maximal to the final term of experiment (28 days). The level of leukocytes in peripheral blood of the main group rats did not exceed the normal value for the given species of animals throughout the follow-up period. The number of eosinophils in the peripheral blood of the rodents of both groups did not differ at every period of survey. Thus, the introduction of the drug reduced the severity of leukocyte response to injury, improvement in postoperative hemoglobin and hematocrit levels

INVOLVEMENT OF JNK MAPK CASCADES IN THE FORMATION OF ADHESIONS IN THE ABDOMINAL CAVITY

Adhesive process in the abdominal cavity is one of the most frequent complications of intra-abdominal surgery.The aim of the study was to evaluate the activation of the JNK MAPK cascade during the experimental adhesion process.Materials and methods. Experimental studies were performed on 40 male Wistar rats (9 months old). We modeled the adhesive  process in the abdominal cavity. At the time from 2 hours (2, 6, 12  hours) to 30 days (1, 3, 7, 14, 30 days), a JNK MAPK cascade was  evaluated in the zone of damage to the serosa using  immunohistochemical methods (painting on JNK1 Phospho (pT183) /  JNK2 Phospho (pT183) / JNK3 Phospho (pT221)) and real-time  PCR (the MAP Kinase Signaling Pathway RT2 - Profiler ™ PCR Array  (Qiagen) kit). Results. We have found that the expression of the  phosphorylated part of the JNK MAPK cascades has an undulating dynamics with two  peaks on the 3rd and 14th day. It has been determined that all  three JNK cascades are involved in the process, and all JNK cascades are synchronously activated on the 3rd day (JNK1 increases 12-fold  in comparison with the group of intact animals, JNK2 is 8-fold, JNK3  is 10-fold). On the 14th day, the activity of the JNK3 cascade is the  most intensively increased – 30 times (for JNK1 – about 6 times,  JNK2 – 12 times).  Conclusion. Significant activation of MARK cascades has been established on the 14th day after traumatic injury, which indicates the need for long-term prevention of posttraumatic changes, in particular, the formation of adhesions

EXPRESSION OF COLLAGENS IN THE DAMAGE AREA AT ABDOMINAL ADHESIONS

Background. Postoperative adhesions are a serious problem in surgery. However, at the present time molecular mechanisms of the adhesion process are insufficiently studied. Aim. To study the dynamics of expression of genes encoding the synthesis of collagen in case of damage to the serosa on the example of the peritoneum in conditions of aseptic inflammation. Materials and methods. Aseptic inflammatory process in the abdominal cavity was modeled (Wistar rats, n = 40). A micro- and macroscopic picture of the damage area was studied. Immunofluorescent staining for Type I collagen (Col 1A1) was performed. The expression of genes encoding collagen of different types was evaluated using the RT2-Profiler PCR kit Array Rat Wound Healing. Results. It has been established that the adhesion process with peritoneal damage in aseptic conditions reaches its maximum by the 30th day of observation. The same period coincides with the maximum of collagen synthesis in fibroblasts in the repair area, revealed by immunofluorescence study. The interrelation of synthesis of type I and III collagens went as expected - the onset of expression of type III collagen (from day 3) is ahead of the expression of collagen type I (from day 7). Peak gene expression of collagens type I, Alpha-1 and -2; type III Alpha-1, type IV Alpha-1 and -3, type V Alpha-1, -2 and -3; type XIV Alpha-1 (Col14a1) falls on the 14th day. For the first time, active involvement of type V alpha-3 collagen in the adhesion process was noted - we detected both early (from day 1) and maximum intensive (up to 166.96 times increase in comparison with intact animals). Conclusion. Perhaps, the hyperexpression of collagen V alpha-3 that we revealed is an important link in the pathogenesis of adhesion in the abdominal cavity