Microflora of patients with purulent septic diseases in the Moscow region

The microflora of clinical material (blood, wound discharge, abdominal exudate, pleural exudate, milk in mastitis, as well as feces in dysbiosis of the large intestine), obtained from patients with purulent septic diseases in the Moscow region was studied. The study revealed the change of microflora from surface biotopes to closed cavities of the body. Gram-positive cocci, primarily coagulase-negative staphylococci, mainly epidermal, were shown to play the leading etiological role in the development of purulent septic diseases. The development of bacteriemia was found to be caused by the penetration of staphylococci from local pyoinflammatory foci (appearing in purulent mastitis, wounds, peritonitis, pleural empyema and pleuritis), as well as by the translocation of staphylococci and Escherichia coli from the large intestine in dysbiosis.     

Diverticulitis with rupture and fatal peritonitis in a Sumatran orangutan (Pongo pygmaeus)

A 30-year-old male Sumatran orangutan (Pongo pygmaeus) presented with signs of depression, lethargy, anorexia, and diarrhea that progressed to acute colic. Exploratory laparotomy revealed fibrinopurulent peritonitis and 50 cm of devitalized small intestine. The surgically resected small intestine contained several mucosal diverticula along the mesenteric attachment; one had ruptured, resulting in peritonitis. Fifteen days after surgery, the orangutan's abdominal incision dehisced. Repeated laparotomy revealed dehiscence of the distal intestinal anastomosis site, as well as extensive adhesions and purulent exudate. The defect was repaired, and the abdomen was extensively irrigated and closed, but the animal died within 24 hours. To our knowledge, this is the first report of diverticulitis in a great ape. Diverticulosis should be considered in the differential diagnosis for great apes that present with signs of depression, lethargy, anorexia, and/or diarrhea.     

Effect of intravascular laser irradiation of blood on the status of the adrenergic and cholinergic structures of the small intestine in experimental peritonitis

In the experiment performed on 60 mongrel dogs the effect of intravascular laser radiation of blood (ILRB) to adrenergic and cholinergic fibers of the small intestine has been studied at treatment of experimental generalized suppurative peritonitis. At treatment of the experimental peritonitis by means of traditional method only one month after its termination a positive reaction to acetylcholinesterase (AChE) is noted, structural organization of cholinergic fibers corresponds to the norm, and density of their plexuses increases. Application of ILRB at treatment of the experimental peritonitis facilitates to increasing density of the cholinergic fibers already on the 21st day after termination of the treatment; their AChE increases essentially, their structural organization corresponds to the norm. In cytoplasm of neurons of the muscular-intestinal plexus a positive reaction to AChE is revealed; this demonstrates their increased functional activity. The small intestine adrenergic apparatus at peritonitis undergoes less manifested structural-chemical alterations. After termination of treatment by means of traditional methods it corresponds to the norm on the 7th day, and after ILBR treatment----on the 3d day. Thus, application of ILBR in treatment of the experimental peritonitis enhances the development of regenerative processes in adrenal and cholinergic structures of the small intestine, facilitates a more manifested demonstration of compensatory-reparative possibilities of the organism.     

Examinations of cell mediated immunity in diffuse peritonitis]

Phagocytic index and rosette test E have been determined in 50 patients, including 15 with diffuse peritonitis and the noncomplicated diffuse peritonitis, 20 patients with septic complications, and 15 patients who underwent abdominal surgery. It was found, that phagocytic index is decreased in all patients after abdominal surgery. The most marked decrease of this index was found in patients with complicated peritonitis. It still decreases in the course of peritonitis and increases in the reference group. The marked decrease in the number of T-cells was observed in complicated peritonitis during the whole period of follow-up while it normalizes in case of noncomplicated peritonitis as in the reference group. Using the tests under study it was possible to assess cell-mediated immunity which is depressed in peritonitis. The tests enable also the prediction of septic complications of peritonitis.     

Microcirculation, hemodynamics and blood rheology in peritonitis during plasmapheresis

By means of biomicroscopy, electrophysiological and hemorheological techniques effect of plasmapheresis with use of various plasma -substituting solutions and their combination on microcirculation, hemodynamics and rheology of blood at peritonitis has been studied in the experiment on 329 white non-inbred rats and on 50 mature dogs. Three periods of disturbances in hemomicrocirculation of the small intestine mesentery at peritonitis have been revealed: I (3-6h)--a relative well-being and compensatory reactions in the system of hemomicrocirculation; II (9-15h)--development of disturbances in the aggregate state of blood; III (18-24h)--pronounced disturbances in hemomicrocirculation. Plasmapheresis at peritonitis facilitates: to better functioning of the microcirculatory system, namely, a sharp increasing of the blood flow rate, joining into the blood flow of capillaries that did not function previously and increasing functional capacity of the capillary bed; decreasing blood viscosity and aggregation of erythrocytes. Plasmapheresis applied at peritonitis produces a favourable effect to hemodynamics, evident as an increasing minute and stroke volume of the blood flow, cardiac index, the left ventricle activity and decrease in peripheral vascular resistance.     

Protection from septic shock by neutralization of macrophage migration inhibitory factor

Identification of new therapeutic targets for the management of septic shock remains imperative as all investigational therapies, including anti-tumor necrosis factor (TNF) and anti-interleukin (IL)-1 agents, have uniformly failed to lower the mortality of critically ill patients with severe sepsis. We report here that macrophage migration inhibitory factor (MIF) is a critical mediator of septic shock. High concentrations of MIF were detected in the peritoneal exudate fluid and in the systemic circulation of mice with bacterial peritonitis. Experiments performed in TNFalpha knockout mice allowed a direct evaluation of the part played by MIF in sepsis in the absence of this pivotal cytokine of inflammation. Anti-MIF antibody protected TNFalpha knockout from lethal peritonitis induced by cecal ligation and puncture (CLP), providing evidence of an intrinsic contribution of MIF to the pathogenesis of sepsis. Anti-MIF antibody also protected normal mice from lethal peritonitis induced by both CLP and Escherichia coli, even when treatment was started up to 8 hours after CLP. Conversely, co-injection of recombinant MIF and E. coli markedly increased the lethality of peritonitis. Finally, high concentrations of MIF were detected in the plasma of patients with severe sepsis or septic shock. These studies define a critical part for MIF in the pathogenesis of septic shock and identify a new target for therapeutic intervention.     

Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis

Intra-abdominal infection in patients following major visceral surgery is associated with high mortality. Using a macrophage depletion technique, we demonstrate that in murine septic peritonitis, Kupffer cells are a major source of systemic IL-10 levels. Kupffer cell-depleted mice were highly susceptible to the lethal effects of septic peritonitis and exhibited an increased bacterial load. Kupffer cell-depleted mice were protected by the administration of an IL-10-Fc fusion protein. Loss of Kupffer cell-derived IL-10 was associated with a weak increase in serum IL-12 levels, whereas TNF, IL-1alpha, and IL-18 levels were not significantly elevated, suggesting that the loss of Kupffer cell-derived IL-10 did not result in a toxic cytokine release syndrome. Instead, loss of Kupffer cell-derived IL-10 was associated with a reduced splenocyte production of IFN-gamma that is required for immune protection in murine septic peritonitis. Therefore, the results suggest that the protective function of IL-10 in septic peritonitis may not be restricted to the anti-inflammatory activities of IL-10.     

The inclusion of ground hay, straw and paper in the diets fed to growing rabbits

In 3 experiments growing rabbits were divided into 2 groups. In each case half received a basal ration while the other half was given this ration supplemented with a ground fibrous material: 20% hay, 10% straw or 10% paper. All the diets were fed in pelleted form. In all the experiments the rabbits fed on the diets containing the added fibrous materials gained in weight slightly more rapidly and had slightly higher food conversion ratios than did those on the control diet, but the differences in the means were not significant. A study of the small intestine and caecum weights expressed as percentages of body weight and as the weights of 1-cm lengths showed that the added fibrous materials increased these weights except in 1 instance where the results were the same. Significant changes were recorded in the case of hay in both the percentage weight and the weight of 1-cm lengths of caecum and in the straw experiment in the weight of 1-cm lengths of small intestine. There were no significant changes in the results from the paper-fed rabbits.     

Type I IFN modulates host defense and late hyperinflammation in septic peritonitis

TLRs are considered important for the control of immune responses during endotoxic shock or polymicrobial sepsis. Signaling by TLRs may proceed through the adapter proteins MyD88 or TIR domain-containing adaptor inducinng IFN-beta. Both pathways can lead to the production of type I IFNs (IFN-alphabeta). In the present study, the role of the type I IFN pathway for host defense and immune pathology in sepsis was investigated using a model of mixed bacterial peritonitis. Systemic levels of IFN-alphabeta protein were markedly elevated during septic peritonitis. More detailed analyses revealed production of IFN-beta, but not IFN-alpha subtypes, and identified CD11b+ CD11c- macrophage-like cells as major producers of IFN-beta. The results further demonstrate that in IFN-alphabeta receptor I chain (IFNARI)-deficient mice, the early recruitment of neutrophils to the infected peritoneal cavity was augmented, most likely due to an increased local production of MCP-1 and leukotriene B4. In the absence of IFNARI, peritoneal neutrophils also exhibited enhanced production of reactive oxygen intermediates and elevated expression of Mac-1. Conversely, administration of recombinant IFN-beta resulted in reduced leukotriene B4 levels and decreased peritoneal neutrophil recruitment and activation. Analysis of the cytokine response to septic peritonitis revealed that IFNARI deficiency strongly attenuated late, but not early, hyperinflammation. In accordance with these findings, bacterial clearance and overall survival of IFNARI(-/-) mice were improved. Therefore, the present study reveals critical functions of the type I IFN pathway during severe mixed bacterial infections leading to sepsis. The results suggest that type I IFN exerts predominantly adverse effects under these conditions.     

Effects of sodium hypochlorite on oxygen balance and functional state of the small intestine in experimental peritonitis]

Sodium hypochlorite, administrated intravenously and intraperitoneally, leads to normal oxygen balance, metabolism and motility of small intestine in peritonitis. Anti-hypoxia effect of this substance is realized by an increase of oxygen content in the blood. It is useful to use sodium hypochlorite in general peritonitis for antibacterial therapy and against tissue hypoxia without side effects.     

Antibiotic therapy in acute diffuse peritonitis]

The pharmacokinetics and clinical efficacy of antibiotics administered by various routes in acute diffuse peritonitis were studied on 25 non-inbred dogs and potential of lymphotropic administration of the antibiotics through the mesentery of the small intestine in urgent surgical operations because of the diseases of the abdominal cavity was estimated. It was shown that the intra-mesenteric administration of the antibiotics was more efficient. In acute diffuse peritonitis it provided high therapeutic concentrations of gentamicin in the central lymph and lymph nodes of the abdominal cavity.     

Morphofunctional changes in the lymph nodes and microcirculatory bed of small-intestinal mesentery of dogs in septic peritonitis after endolymphatic administration of ampicillin

With the aim to study effectiveness+ of endolymphatic (EL) administration of ampicillin (AC), using the model of an acute diffuse septic peritonitis in dogs, the morphological and morphometrical investigation has been performed concerning the state of the lymph nodes (LN), which are regional as regards the pathological focus (pelvic) and remote (tracheobronchial, mesenteric) and hemomicrocirculatory bed (HMCB) of the small intestine mesentery. All LN groups studied are involved in the pathological process, that produces certain increasing disturbances in the structure and cell composition in LN. In 6 h the changes are especially manifested in the pelvic LN, and in 18 h--in the animals without application of AC, or at its intramuscular injection LN lose their typical structure. Their dimensions and number of lymphoid nodules++ and medullary cords decrease, a sharp impoverishment of lymphocytes in LN is observed. By this time critical disturbances in the HMCB structure develop; they are characterized as presence of great amount of avascular areas in the mesentery, extended capillary loops, plasmatic saturation of interstitium. When AC is injected endolymphatically, simultaneously with peritonitis modelling T- and B-dependent zones in LN are preserved, a high volumetric part of lymphocytes is kept in all groups of LN, structure and function of HMCB are normalized. The pronounced delay in development and decreasing manifestation of infective-toxic disorder in LN and HMCB depend on effective concentrations of the antibiotic, produces in the lymphatic system.     

Effect of fluconazole on phagocytic response of polymorphonuclear leukocytes in a rat model of acute sepsis

Recently, fluconazole (FLZ) has been shown to improve survival and reduce multiorgan failure in experimental and clinical septic shock. The mechanism by which FLZ affords protection against sepsis remains obscure. This study examines the effect of FLZ on phagocytic activity of polymorphonuclear leukocytes (PMNs) in a rat model of septic shock by inducing fecal peritonitis in male Wistar rats using intraperitoneal instillation (1 mL/kg) of fecal suspension in saline (1:1 w/v). Sham control rats received sterile fecal suspension and vehicle treatment. FLZ was administered in the doses of 0, 3, 10, and 30 mg/kg by gavage 30 minutes before fecal instillation. The samples of peritoneal fluid were collected 8 hours following fecal inoculation for the evaluation of phagocytic response of PMNs using zymosan-induced luminol-dependent chemiluminescence (CL). Fecal peritonitis caused massive infiltration of PMNs in the peritoneal cavity (ANOVA F(4,45) = 6.322, P < .001). Although FLZ reduced the infiltration of PMNs, this effect was neither significant nor dose dependent. The actual CL response was significantly higher in the peritoneal fluid of rats subjected to peritonitis, which was significantly and dose dependently attenuated by FLZ treatment (ANOVA F(4,45) = 11.048, P < .001). Normalization of CL response for 1000 PMNs revealed that FLZ dose-dependently albeit insignificantly reduced the activity of PMNs. The high dose of FLZ caused 2.29-fold decrement in the area under curve (AUC) pertaining to cumulative CL response. The findings of this study suggest that FLZ protects rats against septic shock by inhibiting PMN-mediated inflammatory cascade without compromising their phagocytic activity.     

Multiple roles for IL-12 in a model of acute septic peritonitis

The present study addressed the role of IL-12 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP). Although CLP surgery induced IL-12 production at 6 and 24 h after surgery, IL-12 immunoneutralization was clearly deleterious in this model: 54% of CLP mice receiving preimmune serum survived, whereas mice administered IL-12 antisera prior to CLP experienced a 25% survival rate. IL-12 immunoneutralization not only led to increased mortality, but also appeared to promote a shift away from IL-12 and IFN-gamma, in favor of IL-10. This cytokine shift corresponded to changes in bacterial load, as CLP mice receiving IL-12 antiserum yielded more CFUs from the peritoneal cavity at 24 h after CLP. To address the role of bacterial infection in IL-12 antiserum-induced mortality following CLP, antibiotics were administered for 4 days after surgery. Despite regular antibiotic administration, IL-12 immunoneutralization still reduced survival in CLP mice. Furthermore, histology of the ceca revealed that mice administered IL-12 antisera failed to show typical organization of the damaged cecum wall. Accordingly, Gram staining revealed bacteria within peritoneal fluids from these mice, while peritoneal fluids from CLP mice that received preimmune serum and antibiotics were free of bacteria. Altogether, these data suggested multiple important roles for IL-12 in the evolution of murine septic peritonitis.     

Neurohistochemical study of intestinal innervation in experimental diffuse peritonitis

In rats with diffuse peritonitis obtained by intraabdominal administration of a 10% fecal suspension (0.8 ml X 100g) neurohistochemical methods were used to study the adrenergic and cholinergic innervation of muscular membrane of the small and large intestine. It is shown that the disturbance of cholinergic innervation comes along with the intestinal paresis. Adrenergic innervation, represented by separate bundles, is found to be slightly affected.     

Cutting edge: myeloid differentiation factor 88 deficiency improves resistance against sepsis caused by polymicrobial infection

Toll-like receptors (TLRs) are important for the activation of innate immune cells upon encounter of microbial pathogens. The present study investigated the potential roles of TLR2, TLR4, and the signaling protein myeloid differentiation factor 88 (MyD88) in polymicrobial septic peritonitis. Whereas both TLR2 and TLR4 were dispensable for host defense against septic peritonitis, MyD88-deficient mice were protected in this infection model. Recruitment of neutrophils to the septic focus and bacterial clearance were normal in MyD88-deficient mice. In contrast, the systemic inflammatory response was strongly attenuated in the absence of MyD88. Surprisingly, MyD88 deficiency did not alter cytokine and chemokine production in spleen, but markedly reduced the inflammatory response in liver and lung. Production of monocyte chemoattractant protein-1 and macrophage-inflammatory protein-1alpha was entirely independent of MyD88. These results imply a central role of MyD88 for the systemic immune pathology of polymicrobial sepsis and show that cytokine production in spleen and induction of certain chemokines are MyD88 independent.     

Recording of the Reticular Motility in Cattle with Experimental and Spontaneous Traumatic Reticuloperitonitis

Using the method described in a previous publication for recording the reticulum action in normal cows the authors have investigated three cows with experimentally produced reticuloperitonitis as well as a group of cows with spontaneous peritonitis under treatment at the stationary clinic. The experimental animals were provided with permanent rumen fistulas. In the three cows with experimentally produced peritonitis the pointed object worked loose spontaneously during the first 24 hrs. The symptoms were mild after the first perforation and became aggravated after further perforations. An abnormally prolonged reticulum interval was recorded immediately after the perforation and continued to be clearly distinguishable for two to three days. In the cows with spontaneous peritonitis, this change was observed only in the acute stage. Prolongation of the second phase of the reticulum was the most pronounced finding from the recordings of the reticular movements, both in the cows with experimental peritonitis and in those in the spontaneous group. The change was at its height after two to seven days, and then subsided gradually in the experimental animals in which repeated recordings had been made. The pressure elevation in reticulum during the contractions was lower both in the animals with experimental peritonitis and in the spontaneous group than in the healthy animals. The cows with reticuloperitonitis also displayed impaired ability to pass the recording catheter from the atrium ruminis to the reticulum.     

斑尾榛鸡消化系统的解剖学观察

对7只斑尾榛鸡(Tetrastes sewerzowi)成体的消化系统进行了解剖、测量。消化管总长(161±21)cm,其中小肠、盲肠分别约占消化管总长的40.2%±3.2%和44.9%±2.4%。嗉囊容量约(42±9)ml。相对于其他体重接近的松鸡科鸟类,斑尾榛鸡的盲肠与小肠之比较大,可能与适应消化高纤维的食物有关。     

The molecular mechanisms of severe typhoid fever.

Salmonella typhi continues to cause severe disease in many parts of the world, its most feared complication being perforation of ulcerated Peyer's patches within the small intestine, leading to peritonitis with associated mortality. The pathogenesis of this process is not well understood. In this article, we present a theoretical mechanism as to how bacterial factors and host immunological mediators within infected tissue might contribute to the observed intestinal pathology, and propose that necrosis of the Peyer's patches observed in typhoid is caused by a mechanism similar to the Shwartzman and Koch reactions.     

Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27?h of faecal peritonitis and to a control condition (n?=?9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6?±?5.3 (placebo) vs. 5.4?±?4.6 (norepinephrine) in controls and 2.7?±?2.1 (placebo) vs. 2.9?±?1.5 (norepinephrine) in septic animals; RCR complex II: 3.5?±?2.0 (placebo) vs. 3.5?±?1.8 (norepinephrine) in controls; 2.3?±?1.6 (placebo) vs. 2.2?±?1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.