Acute Inflammatory Edema Research Articles

Anti-inflammatory Effects of KOTMIN13: A Mixed Herbal Medicine in LPS-stimulated RAW 264.7 Cells and Mouse Edema Models.

Background:A Korean herbal medicine, KOTMIN13, composed of Inula japonica Thunberg, Trichosanthes kirilowii Maximowicz var. japonica kitamura, Peucedanum praeruptorum Dunn, and Allium macrostemon Bge, has been used for anti-allergic and anti-asthmatic treatment in oriental clinics, but its activity has not been investigated.Materials and Methods:To evaluate the anti-inflammatory activity of KOTMIN13 for in vitro study, LPS-stimulated RAW 264.7 cells were used to induce the production and expression of inflammatory mediators and its mechanisms. 12-O-Tetradecanoylphorobol-13 aceate (TPA)-induced ear edema and carrageenan-induced paw edema models were also used to evaluate the effect of KOTMIN13 on acute inflammation in vivo.Results:KOTMIN13 reduced the release of inflammatory mediators [nitric oxide, prostaglandin E2, interleukin (IL)-1β, and IL-6] and the protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Mechanism studies showed the attenuation of LPS-induced NF-κB activation by KOTMIN13 via IκBα degradation abrogation and a subsequent decrease in nuclear p65 levels. Activation of mitogen-activated protein kinases (ERK, JNK, and p38) was also suppressed. Furthermore, KOTMIN13 ameliorated the development of TPA-induced ear edema and carrageenan-induced paw edema in acute inflammatory edema mouse models.Conclusion:Our study demonstrates that KOTMIN13 inhibits inflammatory mediators through the inhibitions of NF-κB and MAPK activities in LPS-induced RAW 264.7 cells, as well as acute inflammation in edema models, indicating that KOTMIN13 is an effective suppressor for anti-inflammatory activities.SUMMARY KOTMIN13 decrease the production of No, PGE2, and proinflammatory cytokine (TNF-∝, IL-1β,IL-6).KOTMIN13 Suppressed the degradation of NF-kβ and IKβα and the phosorylation of MAP Kinases.Topical application of KOTMIN13 reduced mouse ear edema.Oral administration of KOTMIN13 decreased carrageenan-induced paw edema. Abbreviations used: NO: nitric oxide; PGE2: prostaglandin E2; iNOS: inducible NO synthase; COX-2: cyclooxygenase-2; TNF-α: tumor necrosis factor-α; IL: interleukin; NF-κB: nuclear factor kappaB; MAPK: mitogen-activated protein kinases; ERK: extracellular signal regulated kinase; JNK: c-jun N terminal kinase; TPA: 12-O-tetradecanoylphorbol-13-acetate

The biological activity of the composition with glucosamine in the diet of rats in the modeling of cartilage and connective tissue damage

The results of experimental researches of the biological activity and physiological effectiveness of glucosamine consumption, including in the combination with glucose, gelatin and camellia, for rats with damaged cartilage and connective tissue have been presented. Animals of the control group (n=12) received a standard diet. Rats from the 2nd and the 3rd groups in addition to the basic diet during 5 days before and the 48 hours on experiment orally consumed the glucosamine sulphate separately prepared at a dose of 10.98 mg/kg of body weight and respectively in dose 900 mg/kg of nutritional composition (44.6% of treated drinking water, 50% of glucose, 4% of gelatin, 1.22% of glucosamine sulfate, 0.15 and 0.03% of xanthan and guar gums). After modeling acute inflammatory edema, induced by administration of hind paw 0.1 ml of a 10% suspension of kaolin, the amounts of rats claws were measured in each of the tested groups. The results indicated much lesser extent of damage in case of glucosamine sulphate consumption, both independently and in combination with glucose and gums, while comparing with the control group. For the animals of the 2nd and the 3rd groups the maximal volume of rats claws occurred earlier (in the range of 4 hr). Also it was 20.2 and 21.5% less compared with the same index of control animals, which had maximal volume of claws almost during the 5th hour after the injury. It was also found that the animals treated with glucosamine sulfate, both separately and in combination with glucose and gums, restored after simulation of acute inflammatory edema more quickly - the volume of tabs on 48 h after injury was 57 and 64% less comparing with the same index in the control group, respectively. Basing on the presented data, it was confirmed that the glucosamine in a combination with glucose, gums and gelatin had positive effect on metabolic processes in the tissues, joints and there was a rationality of this biologically active nutrient's usage in the production of confectionery products.

Anti-inflammatory potential of probiotic Lactobacillus spp. on carrageenan induced paw edema in Wistar rats

The aim of the present study was to evaluate the anti-inflammatory ability of novel indigenous probiotic Lactobacillus fermentum MCC 2759, L. fermentum MCC 2760 and Lactobacillus delbrueckii MCC 2775 in a carrageenan induced acute inflammatory paw edema model. Probiotic cultures were administered to male Wistar rats via oral route. Carrageenan at a concentration of 1% was injected into hind paw of rats 30min after oral gavage on the 8th day of treatment regimen. Paw thickness (mm), stair climbing activity and motility score were the parameters used to score the inflammatory response. L. fermentum MCC 2759, L. fermentum MCC 2760 and L. delbrueckii MCC 2775 showed significant reduction in paw thickness (P<0.05) showing percentage inhibition of 15.67%, 14.72% and 14.84%, respectively, 24h after carrageenan induction. Probiotic treatment also markedly alleviated the stair climbing and motility score. Histological analysis of tissue sections revealed reduction in cellular infiltration of probiotic and drug treatment groups. Adhesion to resected rat intestinal tissue also showed significant adherence capability (>40%) of the probiotic cultures used. Therefore, L. fermentum MCC 2759, L. fermentum MCC 2760 and L. delbrueckii MCC 2775 may be used as potent anti-inflammatory agents with probiotic health benefits.

OP68 – 2605: Tumefactive demyelinating lesions in juvenile-onset multiple sclerosis

Objective To describe the clinical, imaging and micro-structural metrics of TDLs and chronic MS lesions in patients with juvenile-onset MS. Methods Six patients (2 boys, 4 girls, age 14.7±2.4 years) diagnosed with MS were analyzed for the presence of TDLs and chronic non enhancing MS lesions. The MS lesions were defined by a region of interest encircling the lesion center on 2–3 consecutive slices. Results We report on six patients with 6 TDL, which developed acute neurological symptomatology. The two girls presented with acute ataxia and aphasia, and the two boys with severe ataxia. The two other patients progressed rapidly to develop seizures, became stuporotic and were admitted to the pediatric intensive care unit. Brain MRI demonstrated six TDLs, with a TDL volume of 4.7±0.4 cm 3 (mean ± SD), accompanied by peri-lesional edema and ring enhancement. Analysis of the whole group (10 patients) disclosed 21 chronic non enhancing lesions with a volume of 0.72±0.21 cm 3 . Assessment of DTI metrics of TDL as compared to chronic MS lesions disclosed significant differences: apparent diffusion coefficient (ADC) and radial diffusivity (RD) values (×10 −3 ) were significantly higher in TDLs: for ADC, 1.82±0.05 versus 1.02±0.08 (p Conclusion TDL are a possible presentation of demyelinating disorders, posing a diagnostic and therapeutic dilemma towards neoplastic lesions. The micro-structural analysis of TDL suggests a severe tissue disruption probably due to the acute inflammatory process and edema. The different metrics of chronic lesions suggests a different microstructure due to pro-sclerotic tissue reorganization and reduced edema in chronic MS lesions. Our analysis provides metrical tools that together with MR spectroscopy and perfusion may aid to identify accurately TDLs, potentially sparing young patients unnecessary and possibly debilitating brain biopsy.

Brazilin isolated from Caesalpinia sappan L. inhibits rheumatoid arthritis activity in a type-II collagen induced arthritis mouse model.

BackgroundCaesalpinia sappan L. extracts exhibit great therapeutic potential, and have been shown to have analgesic and anti-inflammatory properties. This study aimed to understand the anti-rheumatoid activity of brazilin that was isolated from ethyl acetate extract of C. sappan L. The evaluations were conducted in mice with type-II collagen-induced arthritis (CIA).MethodsBrazilin was purified via preparative HPLC and identified by mass spectrometry and 1H/13C NMR analysis. DBA/1J mice were divided into four groups (n = 10). Three groups of mice received intradermal injections of inducer bovine type-II collagen (BTIIC; 2 mg/ml in 0.05 ml acetic acid) and 0.1 ml of booster complete Freund’s adjuvant (CFA). A second injection of BTIIC with booster incomplete Freund’s adjuvant (ICFA) was given subsequently after 21 days. On 22nd day, purified brazilin (10 mg/kg body weight) or the disease-modifying anti-rheumatic drug methotrexate (3 mg/kg body weight) was administered intraperitoneally daily or every three days for 21 days, respectively to two groups of mice. At the 42nd day, mice sera were collected, and the levels of pro-inflammatory cytokines and stress enzyme markers in serum were measured using standard immunoassay methods. The microstructure and morphometric analyses of the bones were assessed using high-resolution microfocal computed tomography.ResultsBrazilin isolated from C. sappan reduced the arthritis index score and the extent of acute inflammatory paw edema in CIA-mice. The bone mineral density was significantly (p < 0.05) lower in only-CIA mice, and appeared to increase commensurate with methotrexate and brazilin administration. Brazilin prevented joint destruction, surface erosion, and enhanced bone formation as revealed by microstructural examinations. Brazilin markedly attenuated mouse CIA and reduced the serum levels of inflammatory cytokines including TNF-α, IL-1β, and IL-6.ConclusionsBrazilin purified from C. sappan L. shows protective efficacy in CIA mouse, and may be useful to treat chronic inflammatory disorders including rheumatoid arthritis.

Polyalkylimide filler in human immunodeficiency virus-associated facial lipodystrophy: Ophthalmic complications

Case reportA 54-year-old male, who consulted for acute inflammatory palpebral edema. The patient had HIV infection (on antiretroviral treatment) and an associated facial lipodystrophy that was filled with polyalkylimide in both frontotemporal regions one year before. MRI revealed subcutaneous abscesses in the filled areas, which led to preseptal cellulitis. Complete remission was achieved with antibiotic therapy and monitoring. DiscussionPolyalkylimide is a hydrogel that is recently used as facial filler without FDA approval. Although it was believed to be safe and useful for treating HIV lipodystrophy, it is not exempt from adverse effects (infection, abscesses, granulomas) that can compromise the eye area.

PO-0846 Tumefactive Demyelinating Lesions In Juvenile-onset Multiple Sclerosis

Background The pathogenesis of large demyelinating lesions is still controversial. Atypical tumefactive demyelinating lesions (TDL) associated with acute inflammation, peri-lesional oedema and gadolinium ring enhancement are infrequently described in patients with juvenile-onset multiple sclerosis (MS). Objective To describe the clinical, imaging and micro-structural metrics of TDLs and chronic MS lesions in patients with juvenile-onset MS. Methods Ten patients diagnosed with MS were analysed for the presence of TDLs and chronic non enhancing MS lesions. The MS lesions were defined by a region of interest encircling the lesion centre on 2–3 consecutive slices. DTI images were acquired along 31 independent orientations using a single shot echo-planar imaging sequence. Results Four patients with 6 TDL, developed acute neurological symptomatology. The two girls presented with acute ataxia and aphasia, and the two boys with severe ataxia. Three patients progressed rapidly to develop seizures, became stuporotic and were admitted to the paediatric intensive care unit. Brain MRI demonstrated six TDLs. Analysis of the whole group (10 patients) disclosed 21 chronic non enhancing lesions. Assessment of DTI metrics of TDL as compared to chronic MS lesions disclosed significant differences. Conclusion TDL are a possible presentation of demyelinating disorders, posing a diagnostic and therapeutic dilemma towards neoplastic lesions. The micro-structural analysis of TDL suggests a severe tissue disruption probably due to the acute inflammatory process and oedema. Our analysis provides metrical tools that together with MR spectroscopy and perfusion may aid to identify accurately TDLs, potentially sparing young patients unnecessary and possibly debilitating brain biopsy.

Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa

The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20μg/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis.

Rellenos de polialquilamida en lipodistrofia facial asociada al virus de la inmunodeficiencia humana: complicaciones oftalmológicas

Case reportA 54 year old male, who consulted for acute inflammatory palpebral edema. The patient has HIV infection (on antiretroviral treatment) and an associated facial lipodystrophy that was filled with polyalkylimide in both frontotemporal regions one year before. MRI revealed subcutaneous abscesses in the filled areas, which led to preseptal cellulitis. Complete remission was achieved with antibiotic therapy and monitoring. DiscussionPolyalkylimide is a hydrogel that is recently used as facial filler without FDA approval. Although it was believed to be safe and useful for treating HIV lipodystrophy, it is not exempt from adverse effects (infection, abscesses, granulomas) that can compromise the eye area.

TRPA1 Contributes to the Acute Inflammatory Response and Mediates Carrageenan-Induced Paw Edema in the Mouse

Transient receptor potential ankyrin 1 (TRPA1) is an ion channel involved in thermosensation and nociception. TRPA1 is activated by exogenous irritants and also by oxidants formed in inflammatory reactions. However, our understanding of its role in inflammation is limited. Here, we tested the hypothesis that TRPA1 is involved in acute inflammatory edema. The TRPA1 agonist allyl isothiocyanate (AITC) induced inflammatory edema when injected intraplantarly to mice, mimicking the classical response to carrageenan. Interestingly, the TRPA1 antagonist HC-030031 and the cyclo-oxygenase (COX) inhibitor ibuprofen inhibited not only AITC but also carrageenan-induced edema. TRPA1-deficient mice displayed attenuated responses to carrageenan and AITC. Furthermore, AITC enhanced COX-2 expression in HEK293 cells transfected with human TRPA1, a response that was reversed by HC-030031. This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation.

Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) comprise a spectrum of acute inflammatory pulmonary oedema resulting in refractory hypoxaemia in the absence of an underlying cardiogenic cause. There are multiple pulmonary and extrapulmonary causes and ALI/ARDS patients are a clinically heterogeneous group with associated high morbidity and mortality. Inflammatory injury to the alveolar epithelial and endothelial capillary membrane is a central event in the pathogenesis of ALI/ARDS, and involves degradation of the basement membrane. Matrix metalloproteinases (MMPs) have been implicated in a wide variety of pulmonary pathologies and are capable of degrading all components of the extracellular matrix including the basement membrane and key non-matrix mediators of lung injury such as chemokines and cell surface receptors. While many studies implicate MMPs in the injurious process, there are significant gaps in our knowledge of the role of specific proteases at different phases of injury and repair. This article examines the role of MMPs in injury and repair of the alveolar epithelial-endothelial capillary barrier and discusses the potential for MMP modulation in the prevention and treatment of ALI. The need for further mechanistic and in vivo studies to inform appropriate subsequent clinical trials of MMP modulation will be highlighted.

The effect of alloxan diabetes upon adjuvant-induced arthritis in the rat

Abstract THE relation between inflammation and carbohydrate metabolism has been the subject of several investigations using acute inflammatory models such as the anaphylactoid reaction in the rat (Adamkiewicz &amp; Adamkiewicz, 1959; 1960) and true anaphylaxis in the rat and mouse (Kraus, 1964; Gulbenkian, Yanell Grasso &amp; Tabachnick, 1967; Dhar, Sanyal &amp; West, 1967). These acute inflammatory reactions are depressed by the hyperglycaemia produced by alloxan (Adamkiewicz &amp; Adamkiewicz, 1959; 1960), by 2-deoxyglucose (Goth, 1959), by glucose loading (Dhar &amp; others, 1967) and by glucagon (Lefebvre &amp; Van Cauwenberge, 1962). Using the model of “adjuvant arthritis” in the rat, produced by the injection of Freund's adjuvant (Pearson, 1956), Kellett (1965) showed that this chronic arthritic condition was also suppressed when alloxan diabetes was induced in rats before an injection of adjuvant. The syndrome of adjuvant arthritis occurs in two phases, firstly an acute inflammatory oedema at the injection site which is followed after a latent period of about ten days by a secondary, chronic polyarthritis involving all limbs and the tail. Because of the biphasic course of the inflammation, and the possible dependence of the chronic phase on the prior appearance of an adequate initial phase, we decided to investigate the effect of alloxan diabetes induced at various times during the development of the adjuvant arthritic syndrome.

Moxifloxacin Ameliorates Oleic Acid-induced Acute Lung Injury by Modulation of Neutrophilic Oxidative Stress in Rats

Background: Based on the known immunoregulatory functions of moxifloxacin on phagocytes, the therapeutic effect of moxifloxacin on oleic acid (OA)-induced acute lung in jury (ALI) was investigated. Methods: Moxifloxacin (10 mg/kg) was given to male Sprague-Dawley rats that had been given oleic acid (OA, 30 μL) intravenously. Five hours after OA injection, parameters demonstrating ALI were assessed to measure the effects of moxifloxacin on acute lung injury. Results: The pathological findings of OA-induced ALI's was diminished by moxifloxacin. Through ultrastructural and CeCl3 EM histochemistry, moxifloxacin was confirmed to be effective in decreasing oxidative stress in the lung as well. Indices of ALI, such as lung weight/body weight ratio, protein content in bronchoalveolar lavage fluid, and lung myeloperoxidase were decreased by moxifloxacin. In diaminobenzidine immunohistochemistry, fluorescent immunohistochemistry, and Western blotting of the lung, moxifloxacin had decreased the enhanced expression of secretory phospholipase A 2 (sPLA 2) by OA. Conclusion: We concluded that moxifloxacin was effective in lessening acute inflammatory pulmonary edema caused by OA, by inhibiting the neutrophilic respiratory burst, which was initiated by the activation of sPLA2.

Treatment with dexamethasone or liposome-encapsuled vitamin E provides beneficial effects after chemical-induced lung injury

The pathogenesis of lung injury by exposure to highly toxic sulfur and nitrogen mustards involves alkylating damage of the respiratory epithelium followed by an acute inflammatory response and lung edema. The acute phase is followed by long-term respiratory complications characterized by bronchitis, lung fibrosis, and airway hyperreactivity. In this study, we utilized a mouse model for airway inflammation induced by inhalation exposure to the alkylating nitrogen mustard melphalan, in order to investigate possible beneficial treatment effects by the corticosteroid dexamethasone. In addition, we investigated therapeutic efficacy of liposome-encapsuled vitamin E, an antioxidant formulation previously shown to be efficient in counteracting inflammatory conditions. Influx of inflammatory cells to airways, edema formation, and expression of different cytokines were analyzed 6 and 18 hours after exposure to melphalan. In order to evaluate long-term lung effects, we also investigated collagen deposition and accumulation of lymphocytes at 2 and 4 weeks after exposure. A single intraperitoneal injection of dexamethasone (10 mg/kg body weight) 1 hour after melphalan exposure significantly reduced interleukin (IL)-1 and IL-6 in bronchoalveolar lavage fluid (BALF) and diminished the acute airway inflammation. Our results also indicate that early single-dose treatment with dexamethasone protects against long-term effects observed 2–4 weeks after melphalan exposure, as indicated by reduced lymphocytic response in airways and decreased collagen deposition. Furthermore, our results indicate that also vitamin E (50 mg/kg) reduces acute inflammatory cell influx, and suppresses collagen formation in lung tissue, indicating that this drug could be used in combination with corticosteroids for protection against chemical-induced lung injury.

Efeitos dos exercícios físicos sobre o edema inflamatório agudo em ratos Wistar

Os exercícios físicos têm sido associados a importantes e variados benefícios à saúde, como aqueles relacionados a função imune específica e não-específica, destacando-se, nesta última, o processo inflamatório. Contudo, dependendo do tipo, intensidade, freqüência e duração, os exercícios também podem causar certos prejuízos ao organismo. De fato, estudo prévio mostrou que a hipernocicepção de origem inflamatória, em ratos, foi influenciada pelo protocolo de exercícios físicos realizados em esteira ergométrica. Assim, este trabalho teve como objetivo estudar os efeitos dos exercícios físicos de baixa e alta intensidade sobre a resposta inflamatória aguda. Para isso, foram utilizados ratos machos, adultos, da linhagem Wistar, os quais foram submetidos (grupo treinado) ou não (grupo não treinado) a exercícios em esteira ergométrica. A inflamação aguda foi induzida pela injeção de carragenina-0,5% no coxim da pata posterior esquerda dos ratos, sendo o volume de edema inflamatório agudo mensurado por meio de pletismografia, antes e após 1, 2, 3, 4, 6, 8 e 24 horas da indução do processo inflamatório. A análise estatística dos resultados mostrou aumento significante no volume de edema inflamatório nos momentos H1, H2 e H3 (P&lt;0,01) e nos momentos H4 e H6 (P&lt;0,05) nos animais treinados em baixa intensidade. Entretanto, não ocorreram alterações estatisticamente significantes no volume de edema inflamatório agudo em nenhum dos momentos avaliados (P&gt;0,05) nos animais do grupo treinado em alta intensidade em relação aos não treinados. Concluiu-se, então, que os exercícios físicos de baixa intensidade, em esteira ergométrica, aumentaram o volume de edema inflamatório agudo em ratos, provavelmente ocasionado pelo aumento na síntese e secreção de prostaglandinas e/ou aumento nos níveis plasmáticos das citocinas IL-1, IL-6 e TNF-alfa entre outros fatores. Tal fato não foi observado com os exercícios de alta intensidade, mostrando assim, a influência da intensidade, freqüência e duração dos exercícios sobre este parâmetro inflamatório.

Targeted Disruption of the Galanin Gene Attenuates Inflammatory Responses in Murine Skin

The release of neuropeptides from primary sensory nerve fibers has been implicated in the modulation of local immune responses in surface tissues, such as the skin and the gastrointestinal mucosa, thereby inducing neurogenic inflammation, which is characterized by plasma extravasation and vasodilatation. In addition, cytokines, either alone or in conjunction with neuropeptides, initiate recruitment of immunocompetent cells such as neutrophils during the initial phases of inflammation. Growing evidence suggests that the neuropeptide galanin plays an important role in skin immune defense and pathophysiology. In this paper, we report that adult mice carrying a loss-of-function mutation in the galanin gene (galanin knockout, Gal KO) demonstrate an absence of the normal neurogenic inflammatory response, upon treatment of the skin either with the vanilloid receptor 1 agonist capsaicin or noxious heat. Furthermore, a lack of an acute inflammatory edema induced by coinjection of substance P and calcitonin gene-related peptide was observed. In addition, Gal KO animals also exhibit a deficit in neutrophil accumulation in the skin after exposure to noxious heat, carrageenin, or tumor necrosis factor alpha. These data indicate that Gal KO mice demonstrate abnormal neurogenic inflammatory responses in murine skin compared to strain-matched wild-type mice.

.ALPHA.1-Acid Glycoprotein Suppresses Rat Acute Inflammatory Paw Edema through the Inhibition of Neutrophils Activation and Prostaglandin E2 Generation

Alpha(1)-acid glycoprotein (AGP) is an acute phase protein. Whereas the expression of AGP in an inflammatory state is enhanced by inflammatory cytokines including interleukin-1, 6 (IL-1 and IL-6), and tumor necrosis factor-alpha (TNF-alpha), the biological significance of AGP remains unclear. In the current study, the anti-inflammatory effect of AGP on the acute inflammatory state was examined in vivo and in vitro. AGP suppressed carrageenan-, dextran- and kaolin-induced paw edema and vascular permeability in rat. These results suggest that both initial inflammatory mediators (serotonin and histamine) and later inflammatory mediators (prostaglandin and bradykinin) are involved in the anti-inflammatory effects of AGP. In fact, prostaglandin E(2) (PGE(2)) generation in plasma was significantly inhibited by AGP. Moreover, AGP inhibited the migration of neutrophils treated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) through membrane filter. In addition, AGP significantly suppressed superoxide generation from neutrophils that has been treated with fMLP or phorbol 12-myristate 13-acetate. These results imply that the anti-inflammatory effect of AGP may involve the inhibition of neutrophils migration. The data obtained in this study support a scenario in which an increase in AGP concentration in pathological conditions suppresses inflammation reactions induced by autacoids and neutrophils activities and that AGP plays an important role in the maintenance in the body.

Use of glycyrrhizin in prevention of tissue damage caused by ischemia-reperfusion in rabbit hind limbs

BackgroundGlycyrrhizin, an agent that can bind to selectins and inhibit their ability to bind neutrophils, was found to be effective in preventing tissue edema caused by ischemiareperfusion in a rabbit model. MethodsComplete ischemia was produced by applying a tight Esmarch tourniquet to the hind limbs of 24 Japanese white rabbits. Immediately before and 1h after release of the tourniquet, 12 animals were given glycyrrhizin intravenously; 12 controls received saline. ResultsThe mean relative increase in the circumference of the shins before and after ischemia-reperfusion with or without glycyrrhizin treatment was 4.6%±2.4% and 9.6%±4.2%, respectively, indicating that tissue edema caused by the ischemia-reperfusion was significantly attenuated by glycyrrhizin. Histological studies of cross sections of the anterior tibial muscle 24h after reperfusion showed a significant reduction in the incidence of necrotic muscle fibers in the glycyrrhizin-treated animals compared with the controls that did not receive glycyrrhizin. The mRNA levels of P- and Eselectin 24h after reperfusion were significantly higher in the ischemic anterior tibial muscle than in the nonischemic normal muscle. After 24h of reperfusion, the mean activity of myeloperoxidase, a neutrophil-specific enzyme, in the anterior tibial muscles of the group given glycyrrhizin (0.0022±0.0013 absorbance units) was lower than that of the untreated group (0.027±0.026 absorbance units). ConclusionsThese data suggest that glycyrrhizin treatment is effective in suppressing the acute inflammatory reaction or edema following ischemia-reperfusion and might be potentially useful in clinical practice for preventing ischemiareperfusion injuries to the extremities.

Diazepam effects on carrageenan-induced inflammatory paw edema in rats: Role of nitric oxide

High doses of diazepam (10.0–20.0 mg/kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenan administration. This effect was attributed to an action of diazepam on the peripheral-type benzodiazepine receptor (PBR) present in the adrenal and/or immune/inflammatory cells. The present study was undertaken to analyze the involvement of nitric oxide (NO) on the effects of diazepam on carrageenan-induced paw edema in rats (CIPE) and to look for the presence of PBR and inducible/constitutive NO synthases (NOS) on slices taken from the inflamed paws of diazepam-treated rats. For that, an acute inhibition of NO biosynthesis was achieved using 50.0 mg/kg Nω-nitro- l-arginine ( l-NAME), l-arginine (300.0 mg/kg), the true precursor of NO, and d-arginine (300.0 mg/kg), its false substrate, were also used. The following results were obtained: (1) diazepam (10.0 and 20.0 mg/kg) decreased CIPE values in a dose- and time-dependent way; (2) diazepam effects on CIPE were increased by l-NAME pretreatment; (3) treatment with l-arginine but not with d-arginine reverted at least in part the decrements of CIPE values observed after diazepam administration; (4) PBR were found in endothelial and inflammatory cells that migrated to the inflammatory site at the rat paw; (5) confocal microscopy showed the presence of both PBR and NOS in endothelial and inflammatory cells taken from inflamed paw tissues of rats treated with diazepam a finding not observed in tissues provided from rats treated with diazepam's control solution. These results suggest an important role for NO on the effects of diazepam on CIPE. Most probably, these effects reflect a direct action of diazepam on PBR present in the endothelium of the microvascular ambient and/or on immune/inflammatory cells. An action like that would lead, among other factors, to a decrease in NO, generated by NO synthase, and thus in the mechanisms responsible for CIPE.

The acute Toxicological effects of Gammalin 20 on the lung and Pancreas of Guinea Pig

The acute toxicological effects of Gammalin 20 (gamma Isomer of hexachlorocyclohexane) on the lungs and Pancreas of Guinea Pig were investigated. Twenty-Eight Guinea Pigs of 300gm average body wt were used for the study. Five dose levels 0.0gkg., 0.82gkg –1 ., 1.63gkg -1 ., 3.25gkg -1 and 6.5gkg -1 were obtained after a range finding test using five guinea pigs and administered intra peritoneally, into the animals. Signs and symptoms of toxicity (Irritability, staggering, laboured breathing, convulsion and death) were observed, scored in this order of severity and found to be dose dependent. Histopathological examination of the lungs revealed edema, congestion and disruption of lung architecture. The Pancreas showed acute toxic inflammatory reaction, edema, acute pancreatitis and disruption of Pancreatic architecture. LD 50 of gammalin 20 in the male guinea pig using intraperitoneal route was 1.87gkg -1 . gammalin 20 therefore based on classification of toxicity of chemicals was found to be slightly toxic to the male guinea pig using intraperitoneal route of administration. Journal of Applied Sciences and Environmental Management Vol. 8 (1) 33 - 35