The mc2-CMX vaccine induces an enhanced immune response against Mycobacterium tuberculosis compared to Bacillus Calmette-Guérin but with similar lung inflammatory effects

Although the attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine has been used since 1921, tuberculosis (TB) control still proceeds at a slow pace. The main reason is the variable efficacy of BCG protection against TB among adults, which ranges from 0-80%. Subsequently, the mc2-CMX vaccine was developed with promising results. Nonetheless, this recombinant vaccine needs to be compared to the standard BCG vaccine. The objective of this study was to evaluate the immune response induced by mc2-CMX and compare it to the response generated by BCG. BALB/c mice were immunised with both vaccines and challenged withMycobacterium tuberculosis (Mtb). The immune and inflammatory responses were evaluated by ELISA, flow cytometry, and histopathology. Mice vaccinated with mc2-CMX and challenged with Mtb induced an increase in the IgG1 and IgG2 levels against CMX as well as recalled specific CD4+ T-cells that produced T-helper 1 cytokines in the lungs and spleen compared with BCG vaccinated and challenged mice. Both vaccines reduced the lung inflammatory pathology induced by the Mtb infection. The mc2-CMX vaccine induces a humoral and cellular response that is superior to BCG and is efficiently recalled after challenge with Mtb, although both vaccines induced similar inflammatory reductions.

Vitamin C and endogenous cortisol in foreign-body inflammatory response in pacus

The objective of this work was to evaluate the effect of food supplementation with vitamin C on macrophage and multinucleated giant cell (MGC) activities of pacus at two stocking densities. The experiment was carried out in a 2x2x3 split-plot factorial arrangement with: 0 and 500 mg kg-1 vitamin C; 5 and 20 kg m-3 stocking densities; and evaluation times at 3, 6, and 12 days after the subcutaneous implantation of glass coverslips (DPI). The number of macrophages and MGC, as well as cortisol and glucose plasma levels were determined. The number of macrophages and MGC with two to five nuclei was significantly greater in fish supplemented with vitamin C at 5 kg m-3 stocking density at 3 DPI in comparison to nonsupplemented ones. The macrophage and MGC counts were lower in fish with high-plasma cortisol concentration. Supplementation with 500 mg vitamin C benefits macrophage activity on foreign-body inflammation, and high-cortisol concentration has suppressive effects on this response.

Inflammatory pseudotumor of the hip: a complication of arthroplasty to be recognized by the radiologist

AbstractSoft tissue complications following hip arthroplasty may occur either in cases of total hip arthroplasty or in hip resurfacing, a technique that has become popular in cases involving young patients. Both orthopedic and radiological literatures are now calling attention to these symptomatic periprosthetic soft tissue masses called inflammatory pseudotumors or aseptic lymphocytic vasculites-associated lesions. Pseudotumors are associated with pain, instability, neuropathy, and premature loosening of prosthetic components, frequently requiring early and difficult reoperation. Magnetic resonance imaging plays a relevant role in the evaluation of soft tissue changes in the painful hip after arthroplasty, ranging from early periprosthetic fluid collections to necrosis and more extensive tissue damage.

Correlation of anti-inflammatory activity with phenolic content in the leaves of syzygium cumini (l.) skeels (myrtaceae)

Phenolic contents of extracts of Syzygium cumini leaves, collected monthly over a one-year period, were quantitatively determined by the modified Folin-Ciocalteau method. Extracts and tannin-free fractions were assayed by their potential to inhibit mouse paw edema induced by C48/80. HPLC showed high molecular weight phenolic species and flavonoids in the active extracts and fractions. The highest total phenolic content corresponded to the most potent degree of inhibition and the flavonoids were supposed to be the main species responsible for the activity, given that the flavonoid-enriched ethyl-acetate fraction maintained its effect down to a dose of 0.01 mg/kg in a dose-response manner.

Steroidal and phenolic compounds from Sidastrum paniculatum (L.) Fryxell and evaluation of cytotoxic and anti-inflammatory activities

Sidastrum paniculatum (L.) Fryxell belongs to the family Malvaceae and is popularly known as "malva roxa" or "malvavisco". The phytochemical study of the hexane, CHCl3 and EtOAc phases from the crude ethanol extract of S. paniculatum led to the isolation of six compounds: a mixture of β-sitosterol and stigmasterol, 4-methoxy-3-hydroxybenzoic acid, 4-methoxy-3-hydroxybenzaldehyde, N-trans-feruloyltyramine and kaempferol-3-O-β-D-(6''-E-p -coumaroyl) glucoside. The structural identification of the compounds was made on the basis of spectroscopic methods such as IR, ¹H and 13C NMR with the aid of including two-dimensional techniques, besides comparison with literature data. The β-sitosterol and stigmasterol mixture showed a significant anti-inflammatory activity.

Simultaneous determination of non-steroidal anti-inflammatory drugs in pharmaceutical formulations and human serum by reversed phase high performance liquid chromatography

A rapid and sensitive method using high performance liquid chromatography has been developed and validated for the simultaneous determination of non-steroidal anti-inflammatory drugs (NSAIDs) in pharmaceutical formulations and human serum. Six NSAIDs including: naproxen sodium, diclofenac sodium, meloxicam, flurbiprofen, tiaprofenic and mefenamic acid were analyzed simultaneously in presence of ibuprofen as internal standard on Mediterranea C18 (5 µm, 250 x 0.46 mm) column. Mobile phase comprised of methanol: acetonitrile: H2O (60:20:20, v/v; pH 3.35) and pumped at a flow rate of 1 mL min-1 using 265 nm UV detection. The method was linear over a concentration range of 0.25-50 µg mL-1 (r² = 0.9999).

CHEMICAL CONSTITUENTS, ANTI-INFLAMMATORY, AND FREE-RADICAL SCAVENGING ACTIVITIES OF Guettarda viburnoides CHAM. & SCHLTDL. (RUBIACEAE)

Chemical investigation of Guettarda viburnoides (leaves) led to the isolation of ursolic acid, uncaric acid, secoxyloganin, and grandifloroside, along with a mixture of quercetin-3-O-β-D-galactopyranoside and quercetin-3-O-β-D-glucopyranoside, and of β-sitosterol and stigmasterol. The structures of the isolated compounds were elucidated on the basis of their NMR data. The crude extract, ethyl acetate fraction, aqueous-methanol fraction, and grandifloroside showed significant DPPH free-radical scavenging activities with IC50 ranging from 18.92 to 26.47 µg mL-1. The topical administration of the crude extract and fractions markedly reduced the croton oil-induced mice ear edema in 67.0%-99.0%. Inhibition of tissue MPO activity was also observed, which demonstrated an anti-inflammatory effect of the G. viburnoides species.

CHEMICAL COMPOSITION AND ANTI-INFLAMMATORY ACTIVITY OF Roldana platanifolia

The chemical study of Roldana platanifolia led to the isolation of β-caryophyllene, five eremophilanolides, chlorogenic acid, and a mixture of β-sitosterol-stigmasterol, β-sitosteryl glucopyranoside, and sucrose. The anti-inflammatory activities of the extracts and isolated products were tested using the 12-O-tetradecanoylphorbol-13-acetate (TPA) model of induced acute inflammation. The acetone and methanol extracts showed dose dependent activities (ID50 0.21 and 0.32 mg/ear, respectively), while none of the isolated compounds exhibited relevant edema inhibition. The active extracts were also evaluated with the myeloperoxidase assay technique (MPO) to determine their ability to prevent neutrophil infiltration. Results showed that the anti-inflammatory activity was related to the compound’s ability to inhibit pro-inflammatory mediators such as neutrophils.

Impact of Roux-en-Y gastric bypass on lipid and inflammatory profiles

Objective: To evaluate the behavior of acute phase proteins and lipid profile in patients undergoing Roux-en-Y gastric bypass. Methods : We conducted a prospective study, consisting of three moments: M1 - preoperative (24 hours before surgery); M2 - 30 days after surgery; and M3 - 180 days after surgery. We carried measured height and BMI, as well as determined the concentrations of acute phase proteins (C-reactive protein (CRP), albumin and Alpha-1-acid glycoprotein) and total cholesterol, LDL-c, HDL-c and triacylglycerol. Results : participants comprised 25 individuals, with a mean age of 39.28 ± 8.07, 72% female. At all times of the study there was statistically significant difference as for weight loss and BMI. We found a significant decrease in CRP concentrations between the moments M1 and M3 (p = 0.041) and between M2 and M3 (p = 0.018). There was decrease in Alpha-1-GA concentrations between M1 and M2 (p = 0.023) and between M1 and M3 (p = 0.028). The albumin values increased, but did not differ between times. Total cholesterol and triacylglycerol decreased significantly ay all times. LDL-c concentrations decreased and differed between M1 and M2 (p = 0.001) and between M1 and M3 (p = 0.001). HDL-c values increased, however only differing between M1 and M2 (p = 0.050). Conclusion : Roux-en-Y gastric bypass promoted a decrease in plasma concentrations of CRP and Alpha-1-acid glycoprotein, improving lipid and inflammatory profiles.

Thymic atrophy in cattle poisoned with Solanum glaucophyllum

Solanum glaucophyllum (Sg) [= S. malacoxylon] is a calcinogenic plant inducing "Enzootic Calcinosis" in cattle. The 1,25-dihydroxyvitamin D3, its main toxic principle, regulates bone and calcium metabolism and also exerts immunomodulatory effects. Thymocyte precursors from bone marrow-derived progenitor cells differentiate into mature T-cells. Differentiation of most T lymphocytes is characterized not only by the variable expression of CD4/CD8 receptor molecules and increased surface density of the T cell antigen receptor, but also by changes in the glycosylation pattern of cell surface glycolipids or glycoproteins. Thymocytes exert a feedback influence on thymic non-lymphoid cells. Sg-induced modifications on cattle thymus T-lymphocytes and on non-lymphoid cells were analysed. Heifers were divided into 5 groups (control, intoxicated with Sg during 15, 30 or 60 days, and probably recovered group). Histochemical, immunohistochemical, lectinhistochemical and morphometric techniques were used to characterize different cell populations of the experimental heifers. Sg-poisoned heifers showed a progressive cortical atrophy that was characterized using the peanut agglutinin (PNA) lectin that recognizes immature thymocytes. These animals also increased the amount of non-lymphoid cells per unit area detected with the Picrosirius technique, WGA and DBA lectins, and pancytokeratin and S-100 antibodies. The thymus atrophy found in intoxicated animals resembled that of the physiological aging process. A reversal effect on these changes was observed after suppression of the intoxication. These findings suggest that Sg-intoxication induces either directly, through the 1,25-dihydroxyvitamin D3 itself, or indirectly through the hypercalcemia, the observed alteration of the thymus.

Effects of infection with Toxoplasma gondii oocysts on the intestinal wall and the myenteric plexus of chicken (Gallus gallus)

This paper aims to analyze the effects of the Toxoplasma gondii infection in the intestinal wall and myenteric plexus of chicken (Gallus gallus). Ten 36-day-old chickens were separated into two groups: control and experimental, orally inoculated with oocysts of the T. gondii strain M7741 genotype III. After 60 days the birds were submitted to euthanasia and had their duodenum removed. Part of the intestinal segments was submitted to histological routine, HE staining, PAS histochemical technique, and Alcian Blue. Qualitative analysis of the intestinal wall and comparative measurements among the groups with respect to total wall thickness, muscle tunic, mucosa, and tunica mucosa were carried out. Caliciform cells were quantified. The other part of the intestinal segments was fixed in formol acetic acid and dissected having the tunica mucosa and the tela submucosa removed. Neurons were stained with Giemsa, counted, and measured. Chickens from the experimental group presented diarrhea and inflammatory infiltrates in the tunica mucosa, thickness reduction of all the parameters assessed in the intestinal wall, and an increase of the number of caliciform cells. There was a ~70% reduction regarding the intensity of myenteric neurons; and the remaining cells presented a reduction of ~2.4% of the perikarion and ~40.5% of the nucleus (p<0.05). Chronic infection induced by T. gondii oocysts resulted in intestinal wall atrophy, mucin secretion increase, death and atrophy of chicken myenteric plexus neurons. Death and atrophy of myenteric plexus neurons may be related with the causes of diarrhea observed in chickens with toxoplasmosis.

Equine proliferative enteropathy on a Brazilian farm

Abstract:Lawsonia intracellularis infection on a horse farm in the Midwest region of Brazil is described. Thirty-nine foals a few days to months old from a herd with 300 horses, experienced diarrhea with variable characteristics and intensities, weight loss, hyperemic mucous membranes and dehydration. In foals 3 to 6 months of age, hypoproteinemia associated with submandibular edema were also common. Intestinal fragments of a 7-month-old foal were sent to an animal disease laboratory for diagnosis. The observed macroscopic lesions were hyperemic serosa, thickening of the intestinal wall with a corrugation, thickening of the mucosa folds and reduction of intestinal lumen. Histological analysis of the small and large intestine revealed enterocyte hyperplasia of the crypts associated with diffuse marked decrease in the number of goblet cells and positive L. intracellularis antigen labeling by immunohistochemistry. Three out of 11 animals of the same property were seropositive for L. intracellularis, demonstrating the circulation of the agent throughout the farm, but none were PCR positive in fecal samples. Based on clinical signs and pathological findings, the diagnosis of equine proliferative enteropathy was confirmed.

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

Abstract: With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B at 30mg/kg 6, 12, 18, and 24h after oligofructose) and non-treated groups. Laminar biopsies were performed before and 12, 36, and 72h after administering oligofructose. Samples were stained with periodic acid-Schiff (PAS) and scored from 0 to 6 according to epidermal cell and basal membrane changes. The IL-1β, IL-6, and CXCL1 RNA expressions were determined by RT-PCR. Parametric and non-parametric tests were used to compare times within each group (P<0.05). The PAS grades and IL-1β and IL-6 RNA expression increased in the non-treated group, but remained constant in the treated horses. In conclusion, DF1681B therapy reduced laminar inflammation and epidermal deterioration in treated horses. CXCR1/2 blockage should be considered therapeutically for equine acute laminitis.

Inflammatory and anti-inflammatory effects of soybean agglutinin

Soybean agglutinin (SBA) lectin, a protein present in raw soybean meals, can bind to and be extensively endocytosed by intestinal epithelial cells, being nutritionally toxic for most animals. In the present study we show that SBA (5-200 µg/cavity) injected into different cavities of rats induced a typical inflammatory response characterized by dose-dependent exudation and neutrophil migration 4 h after injection. This effect was blocked by pretreatment with glucocorticoid (0.5 mg/kg) or by co-injection of N-acetyl-galactosamine (100 x [M] lectin), but not of other sugars (100 x [M] lectin), suggesting an inflammatory response related to the lectin activity. Neutrophil accumulation was not dependent on a direct effect of SBA on the macrophage population since the effect was not altered when the number of peritoneal cells was increased or decreased in vivo. On the other hand, SBA showed chemotactic activity for human neutrophils in vitro. A slight increase in mononuclear cells was observed 48 h after ip injection of SBA. Phenotypic analysis of these cells showed an increase in the CD4+/CD8- lymphocyte population that returned to control levels after 15 days, suggesting the development of an immune response. SBA-stimulated macrophages presented an increase in the expression of CD11/CD18 surface molecules and showed some characteristics of activated cells. After intravenous administration, SBA increased the number of circulating neutrophils and inhibited in a dose-dependent manner the neutrophil migration induced by ip injection of carrageenan into peritoneal cavities. The co-injection of N-acetyl-galactosamine or mannose, but not glucose or fucose, inhibited these effects. The data indicate that soybean lectin is able to induce a local inflammatory reaction but has an anti-inflammatory effect when present in circulating blood

Role of mast cell- and non-mast cell-derived inflammatory mediators in immunologic induction of synaptic plasticity

We have previously discovered a long-lasting enhancement of synaptic transmission in mammal autonomic ganglia caused by immunological activation of ganglionic mast cells. Subsequent to mast cell activation, lipid and peptide mediators are released which may modulate synaptic function. In this study we determined whether some mast cell-derived mediators, prostaglandin D2 (PGD2; 1.0 µM), platelet aggregating factor (PAF; 0.3 µM) and U44619 (a thromboxane analogue; 1.0 µM), and also endothelin-1 (ET-1; 0.5 µM) induce synaptic potentiation in the guinea pig superior cervical ganglion (SCG), and compared their effects on synaptic transmission with those induced by a sensitizing antigen, ovalbumin (OVA; 10 µg/ml). The experiments were carried out on SCGs isolated from adult male guinea pigs (200-250 g) actively sensitized to OVA, maintained in oxygenated Locke solution at 37oC. Synaptic potentiation was measured through alterations of the integral of the post-ganglionic compound action potential (CAP). All agents tested caused long-term (LTP; duration ³30 min) or short-term (STP; <30 min) potentiation of synaptic efficacy, as measured by the increase in the integral of the post-ganglionic CAP. The magnitude of mediator-induced potentiation was never the same as the antigen-induced long-term potentiation (A-LTP). The agent that best mimicked the antigen was PGD2, which induced a 75% increase in CAP integral for LTP (antigen: 94%) and a 34% increase for STP (antigen: 91%). PAF-, U44619-, and ET-1-induced increases in CAP integral ranged for LTP from 34 to 47%, and for STP from 0 to 26%. These results suggest that the agents investigated may participate in the induction of A-LTP