Polymorphonuclear Infiltration Research Articles

RETRACTED: Up-regulation of ANXA1 suppresses polymorphonuclear neutrophil infiltration and myeloperoxidase activity by activating STAT3 signaling pathway in rat models of myocardial ischemia-reperfusion injury

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and authors. The authors reported that the paper had been submitted without permission of all authors (specifically Professor Wu). When asked to respond to alleged image manipulation by ‘Hoya camphorifolia’ in Fig. 8B and western blots, they responded that they regret the mistakes in figure 8B and that their technical collaborators could not provide the original images of the Western blots in this paper. The authors apologise for any misconceptions that this paper may have resulted in.

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.

The Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Left-sided Endocarditis: Native vs Prosthetic Valves Endocarditis.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has emerged as a useful diagnostic tool for suspected infective endocarditis (IE) in patients with prosthetic valves or implantable devices. However, there is limited evidence regarding use of 18F-FDG-PET/CT for the diagnosis of native valve endocarditis (NVE). Between 2014 and 2017, 303 episodes of left-sided suspected IE (188 prosthetic valves/ascending aortic prosthesis and 115 native valves) were studied. 18F-FDG-PET/CT accuracy was determined in the subgroups of patients with NVE and prosthetic valve endocarditis (PVE)/ascending aortic prosthesis infection (AAPI). Associations between inflammatory infiltrate patterns and 18F-FDG-PET/CT uptake were investigated in an exploratory ad hoc histological analysis. Among 188 patients with PVE/AAPI, the sensitivity, specificity, and positive and negative predictive values of 18F-FDG-PET/CT focal uptake were 93%, 90%, 89%, and 94%, respectively, while among 115 patients with NVE, the corresponding values were 22%, 100%, 100%, and 66%. The inclusion of abnormal 18F-FDG cardiac uptake as a major criterion at admission enabled a recategorization of 76% (47/62) of PVE/AAPI cases initially classified as "possible" to "definite" IE. In the histopathological analysis, a predominance of polymorphonuclear cell inflammatory infiltrate and a reduced extent of fibrosis were observed in the PVE group only. Use of 18F-FDG-PET/CT at the initial presentation of patients with suspected PVE increases the diagnostic capability of the modified Duke criteria. In patients who present with suspected NVE, the use of 18F-FDG-PET/CT is less accurate and could only be considered a complementary diagnostic tool for a specific population of patients with NVE.

Evidence for Increased Content of PGF2α, PGE2, and 6-keto-PGF1α in Endometrial Tissue Cultures From Heavy Draft Mares in Anestrus With Endometritis

Endometritis is one of the most important causes of infertility in mares. Mares may suffer from endometritis outside the breeding season; however, pathological condition is often undiagnosed in anestrus. The aim of this study was to examine whether the secretion profiles of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2), and a metabolite of prostacyclin I2 (6-keto-PGF1α) differ in endometrial tissue cultures of heavy draft mares in anestrus with endometritis compared to those without endometritis. The endometrial biopsies were collected from 51 heavy draft mares. Inclusion criteria for the control group were absence of endometritis confirmed by histology and no ovarian activity. Inclusion criteria for the experimental group were presence of endometritis showing polymorphonuclear cells and/or lymphocytes infiltration in endometrium and no ovarian activity. Retrospectively, 22 mares were enrolled in this study. The content of PGF2α (P < .05) and PGE2 (P < .001) in the culture medium was distinctly elevated in mares suffering from endometritis, compared to control mares. The relative mRNA abundance responsible for prostaglandins synthesis, that is, PGF2α synthase (PGFS; P < .01), PGE2 synthase (PGES; P < .01), and prostaglandin-endoperoxide synthase (PTGS2; P < .01), were also increased in endometrial tissue of mares with endometritis compared to control mares. The content of 6-keto-PGF1α (P < .0001) in endometrial tissue cultures from mares with endometritis was strikingly elevated compared to those without endometritis; however, plasma concentration of 6-keto-PGF1α was not significantly different between experimental and control groups. This leads to the conclusion that augmented endometrial secretion of PGF2α, PGE2, and 6-keto-PGF1α is associated with endometritis even in mares in anestrus.

Lethal outcome of catastrophic antiphospholipid syndrome despite intensive triple therapy

Catastrophic antiphospholipid syndrome (CAPS), an infrequent autoimmune disease, manifests as a widespread thrombotic disease with multiorgan failure with a 37% mortality rate. We report 39-year-old Caucasian women, medical history of Systemic Lupus Erythematous (SLE) complicated with APS and proliferative glomerulonephritis under dialysis. Patient was admitted at the ICU with septic shock with thoracotomy dehiscence origin. During the ICU stay, extensive lower limbs ulcers with polymorphonuclear infiltrate and steatonecrosis areas in adipose and muscular tissue. Lab studies: anti-β2-glycoprotein-Iantibody was detected. As probable CAPS diagnosis was made, triple therapy with methylprednisolone, immunoglobulin and anticoagulation immediately was started. Serious vasoplegic shock occurs with failure in vasopressor support increment and the patient died. The authors report an APS with rapid progression to catastrophic stage, rare complication that occurs only in 1% of catastrophic APS. In CAPS treatment, a statistical association between triple therapy and the decrease of mortality rate of patients with CAPS was observed, when compared with other combinations or with none of the treatments included in the triple therapy. Although the case had a lethal outcome, the authors emphasize the use of triple therapy in CAPS and the challenge of treating patients with CAPS and infection where the balance between the need for anticoagulation, aggressive immunosuppression and infection control is difficult to manage.

The Healing Effect Of Hyperium Perforatum (St. John’s Wort) On Experimental Alcaline Corrosive Eosephageal And Stomach Burns

The most frequent etiologic cause is alkaline substances. We investigated the protective effects of the plant St. John 's Wort (Hypericum perforatum). We included 42 Wistar albino rats weighing between 200-300 grams and divided into six groups as Group 1: Control, Group 2: Burn+Saline (BS), Group 3: Burn+St. John's Wort (BSJW), Group 4: Burn+Plasebo (BP), Group 5: St. John's Wort (SJW), Group 6: Placebo (P). After 15 days of treatment, esophagus, stomach and liver tissue samples were derived by dissection for histopathologic and biochemical markers. The cytotoxic effects of formulation on fibroblasts is evaluated in vitro on human dermoblast fibroblast line (HDFa, Gibco Invitrogen cell culture, C-013-5C). The weight of the rats increased in Group 1, 3, 4, 6, decreased in Group 2 and did not change in Group 5. In the BSJW group, submucosal collagen accumulation, muscularis mucosa damage, tunica muscularis damage and collagen accumulation in esophagus were similar to the control group but lesser than BS and placebo group. In the stomach, mucosal damage, gastric gland dilatation, submucosal polymorphonuclear infiltration were similar to the control group and lesser than the BS group. The lethal concentration of SJW was 2.58 gr/mL. SJW substrate is effective in protecting the esophagus and stomach in mild to moderate alcali corrosive burns in the subacute period. We should keep in mind the protective effects of STW substrate in alkaline corrosive burns of the gastrointestinal system.

Eosinophilic Ulcer Mimicking Spinocellular Carcinoma

An eosinophilic ulcer is a benign, rare, and self-limiting lesion of uncertain pathogenesis, easily confused with oral carcinoma. A 49-year-old woman, with no risk factors, presented with a lesion of 5 months evolution. During an intraoral examination, a solitary, oval ulcer that was white in color, with a yellowish background, clear borders, sessile base, painful sensation, on the left posterior border of the tongue was evident. An incisional biopsy was performed and the diagnostic hypothesis was squamous cell carcinoma. Histological sections revealed fragments of mucosa coated with ulcerated pavement epithelium. The lamina propria was fibrosed and exhibited areas of mononuclear and polymorphonuclear inflammatory infiltrate rich in lymphocytes and eosinophils in the muscle fibers. The diagnosis was compatible with eosinophilic ulceration, excluding the possibility of a malignant lesion. The treatment included extraction of the tooth that traumatized the area. After 4 months, partial regression of the lesion was observed.

Trypanosoma evansi: ultrastructural cardiac muscle and cardiac microvasculature changes in experimental murine infections

Background: Trypanosoma evansi is the etiologic agent of the equine trypanosomosis, a disease related to the detriment of the extensive bovine farming in the Venezuelan grasslands. Even though macroscopic pathologies such as anemia, pale mucosa, icteric tissues, generalized edema, splenomegaly, liver and renal hypertrophy, abortion, anoestrus, emaciation, lymphadenopathies, striated muscle atrophy as well as epicardiac and endocardiac hemorrhages have been described for infections with the agent, no reports of any heart ultrastructural change in experimental or natural infections induced by Venezuelan T. evansi isolates are available. So, a transmission electron microscopic approach to the problem was needed. This work describes cell features of the cardiac myocyte and the cardiac microvasculature ultrastructure in mice experimentally infected with an equine local isolate of T. evansi, also providing an account of the infection with the mice’s survival. Materials, Methods & Results: NMRI Mus musculus were inoculated with a Venezuelan T. evansi isolate derived from a naturally infected Equus caballus. From day three post-infection, and every other day until the mice’s death, one rodent was randomly killed, the heart apex was isosmotically removed and cut in symmetrical blocks, which were fixed, post-fixed, dehydrated, infiltrated, included, sectioned, contrasted and studied by means of transmission electron microscopy, with the subsequent characterization of the cardiac myocyte and the cardiac microvasculature transformations. The evaluation of the micrographs demonstrated ultrastructural time-increasing harmful mitochondrial alterations that included reduction in the number of mitochondria per cell, decrease in mitochondrial dimensions and lessening of the number of cristae per mitochondrion. Myofibrillar destruction, myofilament loss and atrophy were also evident. In addition, damaging augmentation of the vascular endothelium thickness, appearance of abnormal endothelial projections and caveolae loss were incontestable changes. The presence of trypanosomes in the lumen of the heart capillary system was indubitable; however, neither intra-endothelial nor intra-cardiac myocyte parasites were observed; no inter-tissular parasites were found either. Discussion: The ultrastructural modifications in the muscular heart tissue and in the heart capillaries of experimentally infected mice with a Venezuelan isolate of T. evansi, derived from a feral domesticated E. caballus, were incontrovertible being characterized by the deleterious gradual mitochondrial decline. In such a context, the close relationship between the mitochondrion and the ribosome disposition is related to protein synthesis being associated to diverse functions and stress reactions to non-proper substances like T. evansi, such circumstance could lead to cardiac myocyte mitochondrial deterioration. Additionally, changes in the mitochondrial dimensions and/or the number of cristae/mitochondrion are related to the mitochondrial enzyme activity. The myofilament loss and the myofibrillar destruction reported in this work could derive from the capillary damage per se. The overexpression of serum deprivation protein response induces caveolae deformation and endothelial cell membrane tubulation. The heart’s myodamage could be additionally caused by autoimmunity and/or electrolytic unbalance induced by the trypanosome. The endothelial cell detriment could be the result of a distant effect of parasitic toxic catabolites, intense edema, hypoxia and/or ischemia. The atrophy was put in evidence by a growing volume reduction as a result of myofibril loss probably due to collateral ischemic and hypoxic mechanisms caused by the parasite. Furthermore, the effect due to toxins could cause intramuscular microvasculature damage, hypoxia and fibrillar atrophy.The trypanosomes were present in the cardiac capillary circulation, being able, as an inducible result of the liberation of active materials, to provoke mononuclear and polymorphonuclear infiltration, contributing to the inflammatory response.The subcellular damage in the cardiac myocites and in the cardiac microvascularure, along with the presence of trypanosomes in the coronary circulation, and the lack of association between parasites and cardiac myocites or parasites and cardiac endothelial cells, are attributes with a remarkable pathological meaning since it represents a non described phenomenon of gradual ultrastructural change that take part of the events, resulting in the murine host death through a degenerative mechanism.

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

Macrophages are immune-sensing "big eater" phagocytic cells responsible for an innate, adaptive, and regenerative response. After myocardial infarction, macrophages predominantly clear the deceased cardiomyocyte apoptotic or necrotic neutrophils to develop a regenerative and reparative program with the activation of the lipoxygenase-mediated maresin (MaR) metabolome at the site of ischemic injury. The specialized proresolving molecule and macrophage mediator in resolving inflammation, MaR-1, produced by human macrophages, has potent defining effects that limit polymorphonuclear neutrophil infiltration, enhance uptake of apoptotic PMNs, regulate inflammation resolution and tissue regeneration, and reduce pain. In addition to proresolving and anti-inflammatory actions, MaR-1 displays potent tissue regenerative effects in stroke and is an antinociceptive. Macrophages actively participate in the biosynthesis of bioactive MaR-2, which exhibits anti-inflammatory, proresolving, and atherosclerotic effects. A new class of macrophage-derived molecules, MaR conjugates in tissue regeneration, is identified that regulates phagocytosis and the repair and regeneration of damaged tissue. The presented review provides a current summary of the effect of MaR in resolution pathophysiology, with relevance to a cardiac repair program.-Jadapalli, J. K., Halade, G. V. Unified nexus of macrophages and maresins in cardiac reparative mechanisms.

The protective effect of Montelukast against skeletal muscle ischemia reperfusion injury: An experimental rat model.

Montelukast is a selective leukotriene D-4 receptor antagonist, which specifically and reversibly inhibits cysteinyl leukotriene-1 receptor. The aim of this study was to investigate the protective effect of Montelukast on skeletal muscle reperfusion injury created as acute ischemia-reperfusion (IR) injury in Wistar-albino rats. The study comprised 16 male Wistar-albino rats. The rats were randomly separated into two groups as control (IR) and treatment (IR+Montelukast). Ischemia was obtained using a femoral artery clamp. After reperfusion following a 2-hour ischemia, muscle samples were taken for biochemical and histopathological analyses. Malondialdehyde levels were determined to be at statistically higher levels in the control compared with that in the Montelukast group (p=0.002, p<0.01). The superoxide dismutase levels were determined to be at statistically higher level in the Montelukast group compared with that in the control group (p=0.001, p<0.01). In the histopathological examination of the ischemic muscles, edema, polymorinfiltration and erythrocyte extravasation levels were found to be statistically significant higher in the control group than in the Montelukast group. Edema, polymorphonuclear infiltration, and erythrocyte extravasation levels were observed to be significantly reduced in the treatment group compared with that in the control. In this model of skeletal muscle acute IR injury, the protective effect of Montelukast against skeletal muscle reperfusion injury was emphasized. We concluded that Montelukast could accelerate functional recovery in the extremity by limiting the local and systemic complications caused by reperfusion in cases such as extremity trauma with vascular injuries and extremity surgery with prolonged tourniquet application. However, further experimental and clinical studies are required to confirm this effect.

Histopathology in Periprosthetic Joint Infection: When Will the Morphomolecular Diagnosis Be a Reality?

The presence of a polymorphonuclear neutrophil infiltrate in periprosthetic tissues has been shown to correlate closely with the diagnosis of septic implant failure. The histological criterion considered by the Musculoskeletal Infection Society to be diagnostic of periprosthetic joint infection is “greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at ×400 magnification.” Surgeons and pathologists should be aware of the qualifications introduced by different authors during the last years in the histological techniques, samples for histological study, cutoffs used for the diagnosis of infection, and types of patients studied. Recently, immunohistochemistry and histochemistry studies have appeared which suggest that the cutoff point of five polymorphonuclear neutrophils in five high-power fields is too high for the diagnosis of many periprosthetic joint infections. Therefore, morphomolecular techniques could help in the future to achieve a more reliable histological diagnosis of periprosthetic joint infection.

Actinomicosis primaria intestinal. Informe de un caso en íleon y colon. Revisión de la literatura

Actinomycosis is a chronic, suppurative, inflammatory granulomatous disease caused by gram positive anaerobic filamentous bacteria of the genus Actinomyces, most frequently Actinomyces israelii.We report a case of a 42-year-old male presenting with abdominal pain, a 10kg weight loss and a fixed mass in the epigastrium.Tomography revealed dilatation of the intestinal loops and thickening of the colon walls; the coexistence of these two findings suggested a lymphoproliferative process. The tumour, ileum fragment and colon were surgically removed; these were adherent to the serosal fibro-adipose tissue. Microscopically, abundant polymorphonuclear infiltrate and grains of bacteria compatible with Actinomyces spp.were seen.

Use of Copaifera multijuga for acute corneal repair after chemical injury: A clinical, histopathological and toxicogenetic study

Copaiba oil is widely used in medicine, but there are no reports regarding its application in ophthalmology. Therefore, the objective of this study was to evaluate the clinical, histopathological and toxicogenetic effects of eye drops containing 0.1 and 0.5% of Copaifera multijuga Hayne oil on superficial corneal ulcers induced with alkali in the left eye of rats. For histological analysis, the percent reduction in ulcers and thickness of the corneal epithelium and stroma were evaluated 48 and 72 h after ulcer induction. Additionally, neovascularization and polymorphonuclear infiltration were classified in the stroma. The bone marrow micronucleus test was used for toxicogenetic assessment. None of the animals exhibited clinical signs of immediate ocular discomfort after instillation and the eye drops were harmless to the ocular surface. There was a significant difference in percent ulcer reduction and corneal stroma thickness between animals treated with the C. multijuga eye drops and untreated animals with corneal injury and the negative control, respectively, suggesting a healing effect of the oleoresin. Analysis of the thickness of the corneal epithelium at the two time points showed that the eye drops formulated did not significantly reduce the damage caused by alkali. The same was observed for the treatments with the reference drugs. No difference in stromal neovascularization or inflammatory infiltration was observed between the treated groups. The toxicogenetic results revealed the absence of cytotoxicity and genotoxicity of the treatments. In conclusion, the C. multijuga eye drops did not cause damage to the ocular surface under the present experimental conditions and corneal epithelization was similar to the conventional treatments. These results indicate that eye drops containing C. multijuga oleoresin are a promising option for the treatment of superficial keratitis.

Treadmill Slope Modulates Inflammation, Fiber Type Composition, Androgen, and Glucocorticoid Receptors in the Skeletal Muscle of Overtrained Mice.

Overtraining (OT) may be defined as an imbalance between excessive training and adequate recovery period. Recently, a downhill running-based overtraining (OTR/down) protocol induced the nonfunctional overreaching state, which is defined as a performance decrement that may be associated with psychological and hormonal disruptions and promoted intramuscular and systemic inflammation. To discriminate the eccentric contraction effects on interleukin 1beta (IL-1β), IL-6, IL-10, IL-15, and SOCS-3, we compared the release of these cytokines in OTR/down with other two OT protocols with the same external load (i.e., the product between training intensity and volume), but performed in uphill (OTR/up) and without inclination (OTR). Also, we evaluated the effects of these OT models on the muscle morphology and fiber type composition, serum levels of fatigue markers and corticosterone, as well as androgen receptor (AR) and glucocorticoid receptor (GR) expressions. For extensor digitorum longus (EDL), OTR/down and OTR groups increased the cytokines and exhibited micro-injuries with polymorphonuclear infiltration. While OTR/down group increased the cytokines in soleus muscle, OTR/up group only increased IL-6. All OT groups presented micro-injuries with polymorphonuclear infiltration. In serum, while OTR/down and OTR/up protocols increased IL-1β, IL-6, and tumor necrosis factor alpha, OTR group increased IL-1β, IL-6, IL-15, and corticosterone. The type II fibers in EDL and soleus, total and phosphorylated AR levels in soleus, and total GR levels in EDL and soleus were differentially modulated by the OT protocols. In summary, the proinflammatory cytokines were more sensitive for OTR/down than for OTR/up and OTR. Also, the specific treadmill inclination of each OT model influenced most of the other evaluated parameters.

Exploring virulence and immunogenicity in the emerging pathogen Sporothrix brasiliensis.

Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed between S. brasiliensis and S. schenckii proteomes. Despite great diversity in the immunoblot profiles, antibodies were mainly derived against 3-carboxymuconate cyclase, a glycoprotein oscillating between 60 and 70 kDa (gp60-gp70) and a 100-kDa molecule in nearly 100% of the assays. Thus, our data broaden the current view of virulence and immunogenicity in the Sporothrix-sporotrichosis system, substantially expanding the possibilities for comparative genomic with isolates bearing divergent virulence traits and helping uncover the molecular mechanisms and evolutionary pressures underpinning the emergence of Sporothrix virulence.

Btp Proteins from Brucella abortus Modulate the Lung Innate Immune Response to Infection by the Respiratory Route.

Although inhalation of infected aerosols is a frequent route for Brucella infection in humans, it rarely causes pulmonary clinical manifestations, suggesting a mild or nearly absent local inflammatory response. The goal of this study was to characterize the early innate immune response to intratracheal infection with Brucella abortus in mice and to evaluate whether it is modulated by this pathogen. After infection with 106 CFU of B. abortus, the pulmonary bacterial burden at 7 days post-infection (p.i.) was comparable to the initial inoculum, despite an initial transient decline. Brucella was detected in spleen and liver as early as 1 day p.i. IL-1β and MCP-1 increased at 3 days p.i., whereas IL-12, KC, TNF-α, and IFN-γ only increased at 7 days p.i. Histological examination did not reveal peribronchial or perivascular infiltrates in infected mice. Experiments were conducted to evaluate if the limited inflammatory lung response to B. abortusis caused by a bacterial mechanism of TLR signaling inhibition. Whereas inoculation of E. coli LPS to control mice [phosphate-buffered saline (PBS)/LPS] caused lung inflammation, almost no histological changes were observed in mice preinfected intratracheally with B. abortus (WT/LPS). We speculated that the Brucella TIR-containing proteins (Btps) A and B, which impair TLR signaling in vitro, may be involved in this modulation. After LPS challenge, mice preinfected with the B. abortus btpAbtpB double mutant exhibited a stronger pulmonary polymorphonuclear infiltrate than WT/LPS mice, although milder than that of the PBS/LPS group. In addition, lungs from B. abortus btpAbtpB-infected mice presented a stronger inflammatory infiltrate than those infected with the WT strain, and at day 7 p.i., the pulmonary levels of KC, MCP-1, and IL-12 were higher in mice infected with the mutant. This study shows that B. abortus infection produces a mild proinflammatory response in murine lungs, partially due to immune modulation by its Btp proteins. This may facilitate its survival and dissemination to peripheral organs.

Pulmonary mechanic and lung histology induced by Crotalus durissus cascavella snake venom

This study have analyzed the pulmonary function in an experimental model of acute lung injury, induced by the Crotalus durissus cascavella venom (C. d. cascavella) (3.0 μg/kg - i.p), in pulmonary mechanic and histology at 1 h, 3 h, 6 h, 12 h and 24 h after inoculation. The C. d. cascavella venom led to an increase in Newtonian Resistance (RN), Tissue Resistance (G) and Tissue Elastance (H) in all groups when compared to the control, particularly at 12 h and 24 h. The Histeresivity (η) increased 6 h, 12 h and 24 h after inoculation. There was a decrease in Static Compliance (CST) at 6 h, 12 h and 24 h and inspiratory capacity (IC) at 3 h, 6 h, 12 h and 24 h. C. d. cascavella venom showed significant morphological changes such as atelectasis, emphysema, hemorrhage, polymorphonuclear inflammatory infiltrate, edema and congestion. After a challenge with methacholine (MCh), RN demonstrated significant changes at 6, 12 and 24 h. This venom caused mechanical and histopathological changes in the lung tissue; however, its mechanisms of action need further studies in order to better elucidate the morphofunctional lesions.

Effects of herbal ointment containing the leaf extracts of Madeira vine (Anredera cordifolia (Ten.) Steenis) for burn wound healing process on albino rats.

Aim:Skin burn is a health problem that requires fast and accurate treatment. If not well-treated, the burn will cause various damaging conditions for the patient. The leaf extract of Madeira vine (Anredera cordifolia (Ten.) Steenis), or popularly known as Binahong in Indonesia, has been used to treat various diseases. The purpose of this research is to determine the effects of leaf extracts of Madeira vine (A. cordifolia (Ten.) Steenis) on skin burn healing process in rats as an animal model.Materials and Methods:In this research, there were four treatment groups: G0, G1, G2, and G3, each consisting of five rats. All these rats were given skin burns, using hot metal plates. Then, sulfadiazine was given to G0, 2.5% leaf extract of Madeira vine was given to G1, 5% extract was given to G2, and 10% extract was given to G3, for straight 14 days topically, 3 times a day. At the end of the treatment period, skin excisions were conducted, and histopathological examination was carried out.Result:Microscopic observation on the wound healing process on the collagen deposition, polymorphonuclear infiltration, angiogenesis, and fibrosis showed that G2 had a significant difference with G0, G1, and G3 (p<0.05), while group G0 was significantly different from G1 and G3 (p<0.05). The better burn healing process on G2 allegedly because of the activity of flavonoid, saponin, and tannin, contained in the Madeira vine, which have the antioxidant, anti-inflammatory, and antibacterial effects.Conclusion:The ointment from the 5% leaf extract of Madeira vine (A. cordifolia (Ten.) Steenis) has been proven to be effective to be used for topical burn therapy.

The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint

BackgroundRecent findings support a connection between mitochondrial dysfunction and activation of inflammatory pathways in articular cells. This study investigates in vivo in an acute model whether intra-articular administration of oligomycin, an inhibitor of mitochondrial function, induces an oxidative and inflammatory response in rat knee joints.MethodsOligomycin was injected into the rat left knee joint on days 0, 2, and 5 before joint tissues were obtained on day 6. The right knee joint served as control. Results were evaluated by macroscopy and histopathology and by measuring cellular and mitochondrial reactive oxygen species (ROS), 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation), nuclear factor erythroid 2-related factor 2 (Nrf2), and CD68 (macrophages) and chemokine levels. The marker of mitochondrial mass COX-IV was also evaluated.ResultsThe macroscopic findings showed significantly greater swelling in oligomycin-injected knees than in control knees. Likewise, the histological score of synovial damage was also increased significantly. Immunohistochemical studies showed high expression of IL-8, coinciding with a marked infiltration of polymorphonuclears and CD68+ cells in the synovium. Mitochondrial mass was increased in the synovium of oligomycin-injected joints, as well as cellular and mitochondrial ROS production, and 4-HNE. Relatedly, expression of the oxidative stress-related transcription factor Nrf2 was also increased. As expected, no histological differences were observed in the cartilage; however, cytokine-induced neutrophil chemoattractant-1 mRNA and protein expression were up-regulated in this tissue.ConclusionsMitochondrial failure in the joint is able to reproduce the oxidative and inflammatory status observed in arthritic joints.

The effects of ethanol extract of Berberis vulgaris fruit on histopathological changes and biochemical markers of the liver damage in diabetic rats.

Objective(s):Various studies have shown that the diabetes is associated with liver failure. The objective of this study was determining the effects of Berberis vulgaris fruit on histopathological and biochemical markers of liver in diabetic rats.Materials and Methods:In this experimental study, 60 male Wistar rats weighing 200-250 g with free access to water and ad libitum were randomly divided to five twelve-membered groups including healthy control (group 1), diabetic control (group 2, this two groups received distilled water), treated diabetic positive control (group 3) using dose 150 mg/kg/day metformin, and two groups treated with doses 200 (group 4) and 600 (group 5) mg/kg/BW of B. vulgaris extracts via gavage feeding for 8 weeks. Diabetes mellitus was experimentally induced by one dose injection of alloxan 120 mg/kg. This pre-clinical study was performed on 120 mg/kg alloxan induced diabetic rats.Results:The hepatic steatosis status, liver cholestasis and fibrosis were not changed in group 4 and 5. Glycogen deposition changed mildly and polymorphonuclear neutrophils infiltration changed moderately at group 5. Liver hepatitis changed mildly and severely at group 3 as well as group 5, respectively. Glucose, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase were lower in high dose group compared to other groups.Conclusion:Results suggested that B. vulgaris extract can decrease liver damage by influencing hepatic histopathological and biochemical markers in diabetic rats.