Intense Acute Inflammatory Reaction Research Articles

Characteristics of inflammatory reactions during development of liver abscess in hamsters inoculated with Entamoeba nuttalli

Background Entamoeba nuttalli is an intestinal protozoan with pathogenic potential that can cause amoebic liver abscess. It is highly prevalent in wild and captive macaques. Recently, cysts were detected in a caretaker of nonhuman primates in a zoo, indicating that E. nuttalli may be a zoonotic pathogen. Therefore, it is important to evaluate the pathogenicity of E. nuttalli in detail and in comparison with that of E. histolytica. Methodology/Principal findings Trophozoites of E. nuttalli GY4 and E. histolytica SAW755 strains were inoculated into liver of hamsters. Expression levels of proinflammatory factors of hamsters and virulence factors from E. histolytica and E. nuttalli were compared between the two parasites. Inoculations with trophozoites of E. nuttalli resulted in an average necrotic area of 24% in liver tissue in 7 days, whereas this area produced by E. histolytica was nearly 50%. Along with the mild liver tissue damage induced by E. nuttalli, expression levels of proinflammatory factors (TNF-α, IL-6 and IL-1β) and amebic virulence protein genes (lectins, cysteine proteases and amoeba pores) in local tissues were lower with E. nuttalli in comparison with E. histolytica. In addition, M2 type macrophages were increased in E. nuttalli-induced amebic liver abscesses in the late stage of disease progression and lysate of E. nuttalli trophozoites induced higher arginase expression than E. histolytica in vitro. Conclusions/Significance The results show that differential secretion of amebic virulence proteins during E. nuttalli infection triggered lower levels of secretion of various cytokines and had an impact on polarization of macrophages towards a M1/M2 balance. However, regardless of the degree of macrophage polarization, there is unambiguous evidence of an intense acute inflammatory reaction in liver of hamsters after infection by both Entamoeba species.

Characteristics of inflammatory reactions during development of liver abscess in hamsters inoculated with Entamoeba nuttalli.

BackgroundEntamoeba nuttalli is an intestinal protozoan with pathogenic potential that can cause amebic liver abscess. It is highly prevalent in wild and captive macaques. Recently, cysts were detected in a caretaker of nonhuman primates in a zoo, indicating that E. nuttalli may be a zoonotic pathogen. Therefore, it is important to evaluate the pathogenicity of E. nuttalli in detail and in comparison with that of E. histolytica.Methodology/Principal findingsTrophozoites of E. nuttalli GY4 and E. histolytica SAW755 strains were inoculated into liver of hamsters. Expression levels of proinflammatory factors of hamsters and virulence factors from E. histolytica and E. nuttalli were compared between the two parasites. Inoculations with trophozoites of E. nuttalli resulted in an average necrotic area of 24% in liver tissue in 7 days, whereas this area produced by E. histolytica was nearly 50%. Along with the mild liver tissue damage induced by E. nuttalli, expression levels of proinflammatory factors (TNF-α, IL-6 and IL-1β) and amebic virulence protein genes (lectins, cysteine proteases and amoeba pores) in local tissues were lower with E. nuttalli in comparison with E. histolytica. In addition, M2 type macrophages were increased in E. nuttalli-induced amebic liver abscesses in the late stage of disease progression and lysate of E. nuttalli trophozoites induced higher arginase expression than E. histolytica in vitro.Conclusions/SignificanceThe results show that differential secretion of amebic virulence proteins during E. nuttalli infection triggered lower levels of secretion of various cytokines and had an impact on polarization of macrophages towards a M1/M2 balance. However, regardless of the degree of macrophage polarization, there is unambiguous evidence of an intense acute inflammatory reaction in liver of hamsters after infection by both Entamoeba species.

Association of urodynamics and lower urogenital tract nerve growth factor after synthetic vaginal mesh implantation on a rat model.

By investigating the association of urodynamics and urogenital nerve growth factor (NGF) levels in vaginal mesh surgery, we may be able to associate the likelihood of postoperative lower urinary tract symptoms developing as a result of synthetic mesh implanted for pelvic floor reconstructive surgery. Thirty-eight female Sprague-Dawley rats were divided into three groups: mesh, sham (no mesh), and control. Urodynamic study and NGF analysis of the urogenital tissues were done and results were compared among all groups. The urodynamic studies of the mesh and sham groups were further divided into the 4th and 10th days. A P-value<0.05 was considered statistically significant. All rats survived and no complications were observed during the post-implantation period. Histological evaluation showed intense acute inflammatory reaction on days 4 and 7 in the mesh and sham groups when compared to the control. The mesh group showed a larger area of inflammation as compared to the sham. The NGF levels increased significantly in the mesh and sham groups on the 4th and 10th days when compared to the control (P < 0.001, P < 0.001, respectively). Both the mesh and sham groups had shorter voiding interval and lower voiding volume on days 4 and 10 when compared to the control group (P<0.001, P<0.001, respectively). The magnitude on increasing NGF level and decreasing voiding interval and voiding volume was significantly more on the mesh group than the sham group. A higher level of NGF in the early days post-transvaginal mesh implantation is associated with a shorter voiding interval and a smaller bladder capacity, which represents abnormal lower urinary tract symptoms following transvaginal mesh implantation.

Inhibition of Monosodium Urate Crystal-Induced Inflammation by Withaferin A

Gouty arthritis is a characteristically intense acute inflammatory reaction resulting from the formation of sodium urate crystals in the joint cavity. In the present study, the effect of withaferin A, a steroidal lactone was investigated on monosodium urate crystal-induced inflammation in mice; an experimental model for gouty arthritis and compared it with that of the non-steroidal anti-inflammatory drug, indomethacin. Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-alpha were determined in control and monosodium urate crystal-induced mice. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL). Paw volume, the levels of lysosomal enzymes, lipid peroxidation, and inflammatory mediator tumour necrosis factor-alpha were found to be increased significantly and the activities of antioxidant status were in turn decreased in monosodium urate crystal-induced mice; however these changes were reverted back to near normal levels in withaferin A (30 mg/kg/b.wt, i.p.) treated monosodium urate crystal-induced mice. In addition, beta-glucuronidase and lactate dehydrogenase level were reduced in withaferin A (100microg/ml) treated monosodium urate crystal-incubated polymorphonuclear leucocytes. The present findings clearly indicated that withaferin A exerted a strong anti-inflammatory effect against gouty arthritis.

Evil humors take their toll as innate immunity makes gouty joints TREM‐ble

Acute gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular tophaceous deposits of monosodium urate monohydrate (MSU) crystals. Full-blown acute gouty arthritis is dependent on the influx into the joint space of neutrophils, a cell type normally absent from this locus. Hence, the clinical term “gout,” classically described in the 5th century BC by Hippocrates, was derived in a remarkably prescient manner from the Latin word “gutta,” which literally means “drop.” Specifically, gout was named to reflect the notion of “evil humors” aberrantly seeping into affected joints. Recent advances have revealed the uncanny link between this ancient disease and innate immune inflammatory responses that are phylogenetically primeval. Innate immunity provides a first line of defense against infection via primitive responses that are nonspecific and broad in spectrum (1). Unlike adaptive immune responses, stereotypic innate immune “early induced” responses do not directly induce immunologic memory or lasting protective immunity, consistent in acute gout with the recurrent paroxysmal nature of the disease and the primary role in pathogenesis of “professional phagocytes.” Central to rapid innate immune inflammatory and killing responses is the remarkable capacity of all eukaryotic organisms to recognize the same constituents of microbes (termed pathogenassociated molecular patterns [PAMPs]). Seminal identification of Toll and Toll-like receptors (TLRs) that recognize PAMPs in Drosophila indicates that human innate immune mechanisms for discrimination of nonself PAMPs such as lipopolysaccharide (LPS) and peptidoglycan from self are phylogenetically primordial. The majority of encounters with microorganisms expressing PAMPs do not result in disease, but breaching of tissue barriers by pathogens can stimulate innate immune alternative complement pathway activation, the expression of chemokines and certain other inflammatory cytokines, and uptake of the pathogen by resident and recruited professional phagocytes in a rapid effort to eliminate the noxious agent.

The inflammatory process of gout and its treatment

Gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular deposits of monosodium urate (MSU) crystals. Important recent molecular biologic advances in this field have given us a clear picture of the mechanistic basis of gouty inflammation. The innate immune inflammatory response is critically involved in the pathology of gout. Specifically, MSU crystals promote inflammation directly by stimulating cells via Toll-like receptor signaling and by providing a surface for cleavage of C5 and formation of complement membrane attack complex (C5b-9), culminating in secretion of cytokines, chemokines, and other inflammatory mediators with a dramatic influx of neutrophils into the joint. Despite the detailed mechanistic picture for gouty inflammation, there are no placebo-controlled, randomized clinical studies for any of the therapies commonly used, although comparative studies have demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to indomethacin with respect to controlling acute gouty attacks. In general, the first line of anti-inflammatory therapy for acute gout is nonsteroidal anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib can be used where appropriate. The second line of treatment is glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is effective, partly via induction of adrenal glucocorticosteroids and partly via rapid peripheral suppression of leukocyte activation by melatonin receptor 3 signaling. The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects.

Histopathological and immunological investigations of synthetic fibres and structures used in three prosthetic anterior cruciate ligaments: in vivo study in the rat

Three types of prosthetic anterior cruciate ligaments were investigated by enzymatic and histological analysis of the tissue surrounding each implant and immunologically by a cytofluorometric analysis of T-cell populations in the peripheral blood of rats. Two of the prostheses had a braided construction, one made from polyester and the other from high performance polyethylene fibres. The third type also contained high performance polyethylene fibres, but had been manufactured in a knitted construction (Raschel high performance polyethylene). Five specimens from each prosthesis were implanted intraperitoneally in rats by a trocar for different periods of time up to 4 wk. A control group of rats underwent the surgery, but not the implant. No modification in peripheral T-cell populations was induced by the presence of any implant. Whilst the levels of acid phosphatase and esterase activity appeared to have increased slightly following implantation of any of the prostheses, such increases were not highly significant. Histologically, all three materials induced an intense acute inflammatory reaction at 3 d which gave way to a typical chronic response after 4 wk. The only major difference between the prostheses was that after 4 wk the polyester fibres exhibited less inflammation, and the surrounding tissue was more mature, more vascularized and more densely infiltrated with collagen than with the two high performance polyethylene implants. In conclusion, all three devices provided satisfactory biocompatibility in terms of cellular and healing response.

Correlation between mouse skin inflammation induced by arachidonic acid and eicosanoid synthesis.

We and others have shown that arachidonic acid (AA), when applied topically to ear surfaces, causes an intense acute inflammatory reaction within minutes (as measured by ear thickness). In this study, we have investigated the cellular and biochemical changes associated with this phenomenon and have attempted to correlate these changes with the induction of inflammation. Measurement of vascular permeability by the accumulation of [125I]albumin showed that significant plasma exudation was observed at 15 min in AA-treated ears. Furthermore, the increase in [125I]albumin was time related and was nearly 10-fold greater than control at 1 h. No time-related change in plasma exudation was observed with control ears. Measurement of LTC4 by radioimmunoassay showed that there was a significant increase in LTC4 synthesis at 15 min after AA treatment. Maximal LTC4 synthesis occurred at 15 min and subsequently decreased to 30% of peak level at 30 min. Histological examination and myeloperoxidase measurement indicated that few neutrophils were present at these early time points and suggested that cells other than neutrophils are contributing to LTC4 synthesis. Ear thickness, [125I]albumin accumulation and leukotriene C4 (LTC4) synthesis in AA-treated ears were reduced significantly by topically administered mixed lipoxygenase (LO) and cyclooxygenase inhibitors such as BW755C and phenidone. Therefore, we suggest that AA-induced ear inflammation is a suitable screen for detecting LO inhibitors in vivo.

Importance of the intestinal inflammatory reaction in salmonella-mediated intestinal secretion

The ability of Salmonella typhimurium to invade the intestinal epithelium is essential to the pathogenesis of salmonella-induced intestinal secretion. This invasion is accompanied by an intense acute inflammatory reaction. The present study tests the hypothesis that the acute inflammatory reaction may have a role in the pathogenesis of salmonella-induced secretion. Two groups of rabbits infected with S. typhimurium were studied: normal animals and animals pretreated with nitrogen mustard. Nitrogen mustard depletes the polymorphonuclear leukocyte pool and thereby prevents the formation of an acute inflammatory reaction. In vivo ligated ileal loops were constructed and infected 72 h after nitrogen mustard administration when polymorphonuclear leukocytes were undetectable. Nitrogen mustard treatment markedly inhibited salmonella-induced secretion. Ileal histology in normal animals infected with S. typhimurium revealed an intense acute inflammatory reaction, while in animals pretreated with nitrogen mustard only a rare polymorphonuclear leukocyte was seen. The antisecretory effect of nitrogen mustard was not merely a nonspecific effect since nitrogen mustard treatment did not inhibit cholera toxin-induced secretion and did not alter either ileal morphology nor the activities of various intestinal enzymes in normal animals. Nitrogen mustard also did not alter the virulence of the inoculated S. typhimurium. These data suggest that the mucosal inflammatory reaction induced by salmonella invasion may be important to the pathogenesis of the salmonella secretory process. The mechanism by which the inflammatory reaction stimulates secretion is not known.

Histologic Evaluation of the Effects of Intrasulcular Toothbrushing on Human Sulcular Epithelium

Nineteen young adult Caucasian males had an average Gingival Index Score of 0.47. Each was asked to demonstrate his present method of toothbrushing: thirteen used the scrub method, and six combined the scrub and roll methods. Control gingival tissue specimens were taken from the mandibular left first bicuspid or first molar regions, and the area was allowed to heal for 40 days. Following complete healing, intrasulcular brushing was used in the mandibular left posterior segment, for 30 seconds daily for a period of 40 days. The brushing was done by the investigator on 28 days and by the subjects on 12 days. The average Gingival Index Score following intrasulcular brushing was 0.25. A gingival specimen was taken from the experimental area of the mandibular left second bicuspid region. Histological findings in control specimens from 13 subjects showed parakeratinization for varying distances in the sulcus epithelium apical to the gingival crest. In six specimens a complete absence of sulcus keratinization was observed. The average Inflammatory Index Score was 1.21. Following intrasculcular brushing, 18 specimens showed a parakeratin layer apical to the gingival crest; in 14, it extended the entire length of the coronal sulcular epithelium or apparent clinical sulcus, whereas in four more it extended well beyond the gingival crest into the sulcus. In the six subjects whose control specimens showed an absence of keratin apical to the gingival crest, parakeratinization of part or all of the clinical sulcus was found following intrasulcular brushing. The average Inflammatory Index Score was 1.015. A moderately intense acute inflammatory reaction was observed within the attachment epithelium in three subjects. Possible therapeutic benefits and hazards of intrasulcular brushing are discussed.

Aseptic meningitis due to atheromatous material in the subarachnoid space.

500 mg of sterile pooled human atheromatous material was injected into the cisterna magna of 6 mongrel dogs. Repeated cisternal punctures were done at various intervals until sacrifice from 1 day to 28 days following injection. CSF was obtained for cell count, sugar, protein and analysis in the Technicon 6/60 which measured 14 additional chemical and enzymatic variables. All 6 animals showed a prompt cerebrospinal fluid (CSF) pleocytosis which largely subsided during the first 2 weeks after injection. Increased CSF protein content developed more slowly, but was more prolonged than the pleocytosis. There was a variable decrease in CSF sugar and increase in CSF lactate dehydrogenase, calcium and inorganic phosphorous. Light and electron microscopic studies showed an intense acute inflammatory reaction with marked phagocytosis of the foregin material, probably by arachnoidal cells and moderate edematous changes in the astrocytic processes at the site of injection. During the first 2 weeks after the injection the inflammatory reaction became chronic and the edematous changes in the medulla subsided.

Mechanisms of Shigella pathogenesis

Bacillary dysentery, in its classical form, is a diarrhea! disease characterized by multiple bowel movements containing blood, mucus, and pus. Other frequent manifestations include abdominal pain, fever, and tenesmus and in its severest form, toxemia and hypotension. It has become apparent, however, that not all patients manifest these classical features. As with all enteric infections, the clinical spectrum of disease varies from the asymptomatic carrier to diarrhea, or to frank dysentery. In order to approach an understanding of this disease, two broad areas of pathogenesis must be considered. Firstly, what are the properties and peculiarities of shigella bacilli that permit establishment of the disease? Secondly, what are the anatomic and physiologic sites of abnormality in the intestine, and what mechanisms govern the loss of fluid and blood and cause ulceration of the bowel? Most is known about the disease caused by Sizigella flexneri. It is well established that an essential attribute of shigellae necessary for establishment of disease is the ability of pathogens to invade and multiply within the gastrointestinal mucosa (1-4). Strains of shigellae lacking either of these attributes do not cause disease when fed to either the rhesus monkey or to man (2, 5). Invasion of the colon by the virulent shigellae results in an intense acute inflammatory reaction, with hemorrhage and necrosis of the mucosa with resultant ulceration. These lesions are densely populated with shigellae and are the source of the blood, mucus, and pus characteristic of the dysenteric stool.