Uncoupling of Pro- and Anti-Inflammatory Properties of Staphylococcus aureus

Staphylococcus aureus is a Gram-positive bacterium that is carried by a quarter of the healthy human population and that can cause severe infections. This pathobiosis has been linked to a balance between Toll-like receptor 2 (TLR2)-dependent pro- and anti-inflammatory responses. The relationship between these two types of responses is unknown. Analysis of 16 nasal isolates of S. aureus showed heterogeneity in their capacity to induce pro- and anti-inflammatory responses, suggesting that these two responses are independent of each other. Uncoupling of these responses was corroborated by selective signaling through phosphoinositol 3-kinase (PI3K)-Akt-mTOR and extracellular signal-regulated kinase (ERK) for the anti-inflammatory response and through p38 for the proinflammatory response. Uncoupling was also observed at the level of phagocytosis and phagosomal processing of S. aureus, which were required solely for the proinflammatory response. Importantly, the anti-inflammatory properties of an S. aureus isolate correlated with its ability to modulate T cell immunity. Our results suggest the presence of anti-inflammatory TLR2 ligands in the staphylococcal cell wall, whose identification may provide templates for novel immunomodulatory drugs.     

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

Purpose

This study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions.

Materials and Methods

Sprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 µM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated.

Results

Twenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1.

Conclusion

GLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.     

Anti-inflammatory Effects of Oleanolic Acid on LPS-Induced Inflammation In Vitro and In Vivo

Oleanolic acid (OA) is a triterpenoid known for its anti-inflammatory and anti-cancer properties; however, the anti-inflammatory effects of OA on lipopolysaccharide (LPS)-mediated pro-inflammatory responses have not been studied. Here, we first investigated the possible anti-inflammatory effects of OA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by LPS and the associated signaling pathways. We found that OA inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to HUVECs. OA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocyte migration in vivo. Further studies revealed that OA suppressed the production of tumor necrosis factor-α and activation of nuclear factor-κB by LPS. Collectively, these results suggest that OA has anti-inflammatory effects by inhibiting hyperpermeability, the expression of CAMs, and the adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapeutic agent for vascular inflammatory diseases.     

An In Vitro Investigation of the Anti-Inflammatory Properties of Potassium Humate

In this study the anti-inflammatory potential of potassium humate, derived from bituminous coal, has been investigated in vitro. Exposure of resting and phorbol-12-myristate-13-acetate (PMA) stimulated human neutrophils to potassium humate resulted in a decreased expression of CR3 by activated, but not resting cells, in a dose-related way. Humate also inhibited the adhesion of PMA-stimulated neutrophils to a baby hamster kidney cell line expressing ICAM1 (the CR3 ligand) (BHK331-7). Similar results were obtained using normal BHK cells indicating that this inhibition does not only target specific adhesion molecules on the neutrophil and eosinophil membrane by activated phagocytes, but also affects other mechanisms involved in cell adhesion. Opsonised Sephadex or FMLP/Cyto B-induced degranulation of neutrophils and eosinophils were also decreased by humate treatment. Inhibition of the adhesion of activated phagocytes, as well as inhibition of the release of granule polypeptides, both of which are responsible for tissue damage during inflammatory processes, are attractive targets for anti-inflammatory drugs. Because humate is well tolerated with an excellent safety profile it merits further evaluation in patients suffering from inflammatory conditions.     

Anti-Inflammatory Effect of 3,4-Oxo-isopropylidene-shikimic Acid on Acetic Acid-Induced Colitis in Rats

The present work was done to investigate the possible effects of 3,4-oxo-isopropylidene-shikimic acid (ISA) on acetic acid (AA)-induced colitis in rats. Colitis was induced by intracolonic injection of 6?% AA. Several parameters, including macroscopic score and biochemical parameters, were determined to assess the degree of protection. Biochemical parameters such as myeloperoxidase (MPO) activity, malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and inducible NO synthase (NOS) activities were measured following standard assay procedures. The study showed that treatment of rats for 6?days with ISA (100 and 200?mg/kg) was able to give complete protection against AA-induced colitis. Moreover, biochemical changes were reversed and brought toward control. These results suggest a beneficial effect of ISA against experimental colitis and the possible mechanism of the protective effects may be partly due to an antioxidant action.     

Study on Biocompatibility of Cross-linked Hyaluronic Acid Derivatives

Objective：The cross-linked production, which was prepared by HA and cross-linking agent STMP, EDC, GP through cross-linking reaction, might be used in drug delivery system（DDS）. To ensure the security of clinical application, the excellent properties such as none cell toxicity, nonirritant, none general toxicity, none immunological rejection are necessary. Methods ： In accordance with the request of GB/T 16886.1 on security evaluation of medical biomaterials, cell toxicity test, hemolysis test, intracutaneous stimulation test, acute toxicity test, and hypersensitive test were required. Results： Cell toxicity of HA-STMP, HA-EDC, HA-GP were all less than 1. All hypersensitive tests were eligible. But HA-EDC, HA-GP produced different degrees of slight thrill, slight toxicity, hemolysis rate,which were larger than the standard value. Conclusion：HA-STMP possesses favourable biocompatibility, which is a kind of ideal biomaterials and drug carriers.     

Analgesic and Anti-Inflammatory Properties of Aqueous Extract from Leaves of Solanum Torvum (Solanaceae)

Solanum torvum is used in Cameroonian traditional medicine for the management of pain and inflammation. The present work assesses the pain-killing and anti-inflammatory properties of the aqueous extracts of Solanum torvum leaves. Acetic acid- and pressure- induced pains were reduced by this extract while carrageenan-induced inflammation was inhibited at various doses of the extract. The extract therefore has both analgesic and anti-inflammatory properties.     

Studies on the Anti-Inflammatory,Analgesic and Antipyrexic Activities of Betulinic Acid Derived from Tetracera Potatoria

Background

The anti-inflammatory and anti-nociceptive activity of betulinic acid (BA) was investigated in this study. The triterpene was isolated from the ethyl acetate extract of Tetracera potatoria and its structure was verified by IR and NMR spectroscopy. The bioactivity of this compound was assessed using carrageenan-induced paw oedema in rats and carrageenan-induced pulmonary oedema in mice for the anti-inflammatory activity, while acetic acid-induced writhing test in mice and zymosan-induced fever in rats were used for analgesic test.

Materials and Methods

Rats and mice were randomly divided into groups of five animals. For each experiment, betulinic acid at 10, 20 or 40mg/kg b.w was administered intraperitoneally to the first three groups respectively. The fourth group was administered with indomethacin (10mg/kg) or acetylsalicylic acid (150mg/kg), while the fifth group was administered with distilled water (10ml/kg). Data obtained were expressed as mean±S.E.M and significant differences were determined at p<0.05.

Results

BA significantly reduced carrageenan-induced paw oedema by 11.0%, 45.7%, 68.6% or pulmonary oedema by 25.6, 29.2 and 45.13% dose dependently. 40 mg/kg of BA inhibited paw oedema by 68.6% comparably to acetylsalicylic acid (71.4%) or indomethacin (51.33%) respectively. Abdominal writhing was also significantly (p<0.05) reduced to 17.20 writhes by BA (40mg/kg) comparable to Indomethacin (16.3writhes). Fever was inhibited by BA most significantly by 3hours post-injection of zymosan (1.00, 1.45, 0.00°C) and this inhibitory effect was higher than that observed for acetylsalicylic acid (0.30°C).

Conclusion

Betulinic acid derived from Tetracera potatoria exhibited potent anti-inflammatory, analgesic or antipyrexic activity which is comparable to indomethacin or acetylsalicyclic acid.     

Measurement of Cyclooxygenase Inhibition in vivo: A Study of Two Non-Steroidal Anti-Inflammatory Drugs in Sheep

The anti-inflammatory effects of the non-steroidal anti-inflammatory drugs phenylbutazone (PBZ) and flunixin meglumine (FM) and the relationship between the effects and drug concentration in vivo were studied using a subcutaneous tissue-cage model in sheep. Intracaveal injection of carrageenan induced prostaglandin (PG) E₂production in tissue-cage exudate (maximal concentration, 101 nM) with significant increases in white blood cell (WBC) numbers, skin temperature over the inflamed cage and exudate leukotriene B₄ (LTB₄) concentration (P < 0.05). Intravenous PBZ, 4.4 mg kg^–1 produced mild inhibition of exudate PGE₂ generation (10%), but greater inhibition of serum TXB₂ (75.3%). The IC₅₀ for TXB₂ was 36.0 M. Phenylbutazone did not alter effects on skin temperature, WBC numbers or exudate LTB₄ concentrations. Intravenous FM, 1.1 mg kg^–1, significantly inhibited carrageenan-induced exudate PGE₂ formation (E_max, 100%, IC₅₀, <0.4 nM) and serum TXB₂ generation (E_max, 100%, IC₅₀, 17 nM) for up to 32 h. Flunixin meglumine significantly inhibited the rise in skin temperature but had a limited effect on exudate WBC. Phenylbutazone and FM have distinct effects on carrageenan-induced cyclooxygenase (COX-2) and platelet COX (COX-1). Flunixin meglumine was a more potent COX inhibitor than PBZ and was more selective for the inducible form of COX in vivo.     

Solution Properties and Complexation of Polyampholytes based on N,N‐Dimethyldiallylammonium Chloride and Maleic Acid or Alkyl (Aryl) Derivatives of Maleamic Acids

Summary: Solution properties of alternating polyampholytes based on N,N‐dimethyldiallylammonium chloride and maleic acid as well as N,N‐dimethyldiallylammonium and maleamic acid (butylmaleamic acid, phenylmaleamic acid, 4‐butylphenylmaleamic acid) were studied in aqueous and aqueous‐salt solutions. The isoelectric points (IEP) of the amphoteric macromolecules were determined. It was found that the viscosity of equimolar polyampholyte solutions increases at the IEP with an increase in neutral salt concentration, while polyampholyte solutions having an excess of cationic groups exhibit polyelectrolyte character. The influence of pH, neutral salt, and a water–ethanol mixture on the viscosity of polyampholyte solutions was shown. Formation of interpolyelectrolyte complexes between regular polyampholytes based on N,N‐dimethyldiallylammonium chloride–alkyl (aryl) substituted maleamic acids and poly(acrylic acid), poly(styrene sodium sulfonate), as well as the formation of polyampholyte–sodium lauryl sulfate complexes was studied in aqueous solution by potentiometric, conductimetric, turbidimetric, and viscometric methods. The composition of polyampholyte–polyelectrolyte and polyampholyte–surfactant complexes was determined and the influence of temperature and ionic strength on their behavior was studied.

Possible conformational changes of APA‐2 and APA‐3 in water, a water–ethanol mixture, and in ethanol containing 0.15 N KCl.     

The Effects of Two Non-Steroidal Anti-Inflammatory Drugs,Bromfenac 0.1% and Ketorolac 0.45%, on Cataract Surgery

Purpose

To compare the additive effects of two types of non-steroidal anti-inflammatory drugs (NSAIDs), bromfenac 0.1% or ketorolac 0.45%, relative to topical steroid alone in cataract surgery.

Materials and Methods

A total 91 subjects scheduled to undergo cataract operation were randomized into three groups: Group 1, pre/postoperative bromfenac 0.1%; Group 2, pre/postoperative preservative-free ketorolac 0.45%; and Group 3, postoperative steroid only, as a control. Outcome measures included intraoperative change in pupil size, postoperative anterior chamber inflammation control, change in macular thickness and volume, and ocular surface status after operation.

Results

Both NSAID groups had smaller intraoperative pupil diameter changes compared to the control group (p<0.05). There was significantly less ocular inflammation 1 week and 1 month postoperatively in both NSAID groups than the control group. The changes in central foveal subfield thickness measured before the operation and at postoperative 1 month were 4.30±4.25, 4.87±6.03, and 12.47±12.24 µm in groups 1 to 3, respectively. In the control group, macular thickness and volume increased more in patients with diabetes mellitus (DM), compared to those without DM. In contrast, in both NSAID groups, NSAIDs significantly reduced macular changes in subgroups of patients with or without DM. Although three ocular surface parameters were worse in group 1 than in group 2, these differences were not significant.

Conclusion

Adding preoperative and postoperative bromfenac 0.1% or ketorolac 0.45% to topical steroid can reduce intraoperative miosis, postoperative inflammation, and macular changes more effectively than postoperative steroid alone.