共查询到20条相似文献,搜索用时 31 毫秒
1.
Matsuba S Matsuno H Sakuma M Komatsu Y 《Evidence-based complementary and alternative medicine : eCAM》2008,5(1):85-90
Phellinus linteus is a fungus distributed throughout Japan, Korea and China. Boiled water-soluble extracts from P. linteus (PLW) have shown anti-tumor and immunomodulatory properties in experiments done by intraperitoneal treatment, or in in vitro cell cultures. This is the first investigation on how oral administration of PLW influences immune responses. Here, we established immunodeficient mice by mitomycin C (MMC) and then researched how PLW influenced plaque-forming cell (PFC) production and populations of cytokine [interferon- (IFNgamma-) and interleukin-4 (IL-4)]-producing T lymphocytes. PLW samples were administered orally for 19 days (1, 2 or 4 g/kg/day). PFC assay was followed using Jerne's method. IFN- and IL-4-producing T lymphocyte populations were measured by flow-activated cell sorter (FACS). These assays were conducted the day after the last oral administration. MMC groups were given MMC (1 mg/kg/day) intraperitoneally for 6 days with PLW administration. The number of PFC per 10(6) spleen cells increased significantly in the PLW (2 g/kg/day) group when compared with the MMC-control (P < 0.05) while populations of IFNgamma- and IL-4-producing T lymphocytes decreased by MMC treatment. However, the PLW group tended to increase more than the MMC-control. Our results indicated that PLW augments the immune response of the spleen in MMC-induced immunodeficient mice. 相似文献
2.
S H Hong M S Kim J Y Lee C Y Hwang S H Baek D S Han W Y Jung S B Seo T Kajiuchi H M Kim 《Clinica chimica acta; international journal of clinical chemistry》2001,309(1):85-90
This report describes an inhibitory effect of Gahmi-Shini-San (GSS) on mast cell-mediated immediate-type allergic reactions. GSS is an Oriental herbal medication, which has been successfully used in Korea for the treatment of allergic disorders, mainly skin anaphylactic diseases. GSS inhibited the ear swelling response induced by intradermal injection of compound 48/80 in a mouse model on a concentration-dependent basis. The mast cells in mouse ear tissue were stained by alcian blue/nuclear fast red. GSS significantly inhibited the compound 48/80-induced degranulation from mast cells in ear tissue. GSS dose-dependently inhibited the histamine release from the rat peritoneal mast cells by compound 48/80. We also studied the effect of GSS on mast cell-dependent passive cutaneous anaphylaxis activated by dinitrophenyl IgE antibody. GSS showed inhibition of passive cutaneous anaphylaxis following oral administration. These results indicated that GSS has inhibitory effect on mast cell-dependent immediate type cutaneous reactions. 相似文献
3.
Saso Y Conner EM Teegarden BR Yuan CS 《The Journal of pharmacology and experimental therapeutics》2001,296(1):106-112
A specific and potent inhibitor of S-adenosyl-L-homocysteine (AdoHcy) hydrolase, 9-[(1'R,2'S,3'R)-2', 3'-dihydroxycyclopentanyl]adenine (DHCaA), was evaluated for its immunosuppressive efficacy on murine T-cell proliferation in vitro and in several animal models, including delayed type hypersensitivity ear swelling and peptidoglycan polysaccharide-induced arthritis. The concanavalin A-induced [(3)H]thymidine incorporation into T cells was strongly inhibited by DHCaA with a 50% inhibition concentration (IC(50)) of 0.3 microM. In vivo, a dose-dependent reduction (39, 62, and 73%) of ear swelling was observed when 2,4-dinitrofluorobenzene-treated mice were orally administered with DHCaA at 1, 5, and 10 mg/kg, respectively. This inhibition in ear swelling dose dependently corresponded to the inhibition of AdoHcy hydrolase activity in the spleen. The more potent the AdoHcy hydrolase inhibitor, the stronger the immunosuppressive efficacy observed. In rat peptidoglycan polysaccharide-induced arthritis, orally dosed DHCaA significantly suppressed inflamed paw volumes with minimal effective dose of 0.1 mg/kg. At a dose of 1 mg/kg, DHCaA almost completely inhibited paw swelling. This inhibition of paw swelling was associated with an inhibition of interleukin-1beta production in joint tissues. Histopathological evaluation of the joints in rats treated with 1 mg/kg showed a significant improvement in the reduction of the histopathological grading score from untreated scores of 10.44 to 4. 78. Results from this study indicate that inhibitors of AdoHcy hydrolase could be effective anti-inflammatory agents. 相似文献
4.
Inokuchi Y Shimazawa M Nakajima Y Suemori S Mishima S Hara H 《Evidence-based complementary and alternative medicine : eCAM》2006,3(1):71-77
Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retina in vitro and/or in vivo. In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin-reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In mice in vivo, propolis (100 mg kg(-1); intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitreal in vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage both in vitro and in vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects. 相似文献
5.
《The Journal of experimental medicine》1994,179(4):1397-1402
Interleukin 10 (IL-10) is released during the induction phase of contact sensitivity and was shown in prior functional studies to convert epidermal Langerhans cells (LC) from potent inducers of primary immune responses to specifically tolerizing cells in vitro. To investigate whether IL-10 also subserves the function of a tolerizing agent in vivo ears of BALB/c or C3H mice were injected intradermally with 1-2 micrograms of recombinant mouse (rm)IL-10 8 h before epicutaneous application of 3% trinitrochlorobenzene (TNCB; a contact allergen). As a control, mice were injected with phosphate-buffered saline or IL-10 plus neutralizing amounts of anti-IL-10 mAb. 5 d later, mice were challenged with 1% TNCB on contralateral ears and ear swelling response was measured 24 h later. Whereas control-treated mice showed a normal ear swelling response to epicutaneous challenge (delta mm-2 = 25 +/- 5), ear swelling response of IL-10-treated animals was significantly inhibited (delta mm-2 = 3 +/- 2). Coinjection of IL-10- specific mAb together with rmIL-10 completely abrogated this effect. To differentiate between a state of nonresponsiveness and induction of tolerance by IL-10, mice initially treated with IL-10 and TNCB were resensitized with 3% TNCB in the absence of any treatment after 14 d of rest (group 1). Again mice were challenged 5 d later and ear swelling responses were tested. Whereas control mice treated with allergen alone (group 2) showed a good swelling response (delta mm-2 = 28 +/- 6), IL- 10-treated mice (group 1) showed a minimal response towards application of allergen (delta mm-2 = 4 +/- 2). To show that anergy induction by IL- 10 was antigen-specific, mice initially treated with IL-10 plus TNCB were exposed to 0.5% dinitrofluorobenzene (DNFB) 14 d later (group 1). After challenge with 0.1% DNFB, IL-10-treated mice showed an ear swelling response (delta mm-2 = 13 +/- 3; group 1) similar to that of control mice only sensitized with DNFB (delta mm-2 = 14 +/- 3; group 3). In an attempt to show the induction of antigen-specific tolerance in these mice in vitro, regional lymph nodes of mice initially treated with TNCB plus IL-10 (group 1) and control-treated mice (groups 2 and 3) were prepared and cultured in the presence of TNBS, dinitrobenzene sulfonate (DNBS), or medium to measure antigen-specific proliferation.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
6.
映山红总黄酮抗炎作用的实验研究 总被引:12,自引:0,他引:12
目的研究映山红总黄酮(TFR)的抗炎作用及其可能的机制。方法通过二甲苯致小鼠耳肿胀和蛋清致大鼠足爪肿胀模型观察TFR的抗炎作用,并测定大鼠血清和足爪组织中一氧化氮(NO)、丙二醛(MDA)、前列腺素E2(PGE2)的含量和一氧化氮合酶(NOS)活性。结果50、100 mg/kg的TFR能明显抑制二甲苯致小鼠耳片肿胀;25、50、100 mg/kg的TFR可显著抑制蛋清致大鼠足爪的肿胀;在蛋清诱导大鼠足爪肿胀模型中,TFR使血清和脚爪组织屮MDA含量减少,同时脚爪组织中NOS活性、NO和PGE2含量也有显著的下降。结论TFR有一定的抗炎作用,其作用可能与抑制PGE2和NO合成及抗脂质过氧化有关。 相似文献
7.
原花青素的抗炎作用及其作用机制探讨 总被引:1,自引:0,他引:1
目的研究原花青素的抗炎作用及其作用机制。方法以二甲苯致炎小鼠耳片肿胀及角叉菜胶诱发大鼠足爪肿胀模型,分别探讨原花青素对小鼠耳片肿胀及大鼠足爪肿胀的抑制作用。用紫外分光光度法测定足爪炎性渗出液中前列腺素E2(prostaglandin E2,PGE2)的含量。Westerm Blot法和免疫组化法(immunohistochemistry,IHC)检测大鼠足爪中环氧合酶-2(Cyclooxygenase-2,COX2)的表达情况。结果10mg/kg和20mg/kg的原花青素抑制二甲苯致炎小鼠耳片肿胀,原花青素5mg/kg和20.0mg/kgi p在2~5h抑制角叉菜胶诱导的大鼠足爪肿胀。原花青素5mg/kg和20.0mg/kgip能抑制大鼠炎症足爪组织PGE2的生物合成。原花青素5mg/kg和20.0mg/kgip能明显下调COX-2的表达。结论原花青素具有较强的抗炎作用,其抗炎作用可能与抑制COX-2的表达继而下调PGE2的生物合成有关。 相似文献
8.
Tohda C Nakayama N Hatanaka F Komatsu K 《Evidence-based complementary and alternative medicine : eCAM》2006,3(2):255-260
We aimed to compare the anti-inflammatory activities of six species of Curcuma drugs using adjuvant arthritis model mice. When orally administered 1 day before the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling and the serum haptoglobin concentration in adjuvant arthritis mice. Also when orally administered 1 day after the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling. Other Curcuma species (Curcuma longa, Curcuma wenyujin, Curcuma kwangsiensis, Curcuma zedoaria and Curcuma aromatica) had no significant inhibitory effects on adjuvant-induced paw swelling. Cyclooxygenase (COX)-2 activity was significantly inhibited by the methanol extract of C. phaeocaulis. Curcuminoids' (curcumin, bis-demethoxycurcumin and demethoxycurcumin) were rich in C. longa, but less in C. phaeocaulis and C. aromatica, not in C. wenyujin, C. kwangsiensis and C. zedoaria, suggesting that curcuminoids' contents do not relate to inhibition of arthritis swelling. Therefore, C. phaeocaulis may be a useful drug among Curcuma species for acute inflammation, and the active constituents of C. phaeocaulis are not curcuminoids. 相似文献
9.
Aminimanizani A Beringer PM Kang J Tsang L Jelliffe RW Shapiro BJ 《The Journal of antimicrobial chemotherapy》2002,50(4):553-559
Aminoglycosides are often prescribed as part of the treatment regimen for acute pulmonary exacerbations due to their potent activity and low potential for development of resistance. Preliminary evidence from randomized controlled trials in patients with cystic fibrosis (CF) suggests that once-daily administration of aminoglycosides results in similar efficacy and a low risk for toxicity compared with traditional dosing. The pharmacokinetics of aminoglycosides administered once daily in CF patients are currently not well described. In this study we compare the distribution and elimination patterns of traditional dosing (3.3 mg/kg q8h) versus once-daily dosing (10 mg/kg q24h) of tobramycin in six adult patients with CF. The pharmacokinetics of tobramycin administered either once daily or every 8 h were best described by a two-compartment model. No statistically significant differences in any of the pharmacokinetic parameter values between regimens were noted. The distribution phase half-lives of 32 and 24 min following the q8h and q24h regimens were longer than expected. The use of a one-compartment model requires clinical peak levels to be drawn 2 h after initiation of either a 30 min infusion for multiple daily dosing or a 60 min infusion with once-daily dosing, to ensure completion of the distribution phase. Our data indicate that a dose of 10 mg/kg/day provides post-distributional phase peak concentrations that achieve the desired goal for susceptible organisms (>20 mg/L) and AUC(24) values at the upper end of the desired range (70-100 mg.h/L). 相似文献
10.
Activity of lipid-soluble inhibitors of dihydrofolate reductase against Pneumocystis carinii in culture and in a rat model of infection. 总被引:4,自引:10,他引:4
S F Queener M S Bartlett M A Jay M M Durkin J W Smith 《Antimicrobial agents and chemotherapy》1987,31(9):1323-1327
Trimetrexate and BW301U (piritrexim isethionate), lipid-soluble inhibitors of dihydrofolate reductase, are potent inhibitors of the growth of Pneumocystis carinii in culture with WI-38 cells. Inhibition was observed with 0.1 microgram of trimetrexate or BW301U per ml. Trimethoprim is ineffective at 100 micrograms/ml in this culture system. Both trimetrexate and BW301U were effective as prophylactic agents against P. carinii pneumonia in rats; trimetrexate at 7.5 mg/kg protected 9 of 10 rats, and BW301U at 5 mg/kg protected 4 of 10. 相似文献
11.
Efficacies of KY62 against Leishmania amazonensis and Leishmania donovani in Experimental Murine Cutaneous Leishmaniasis and Visceral Leishmaniasis
下载免费PDF全文
![点击此处可从《Antimicrobial agents and chemotherapy》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hail M. Al-Abdely John R. Graybill Rosie Bocanegra Laura Najvar Eleanor Montalbo Steven L. Regen Peter C. Melby 《Antimicrobial agents and chemotherapy》1998,42(10):2542-2548
Current therapy for leishmaniasis is unsatisfactory because parenteral antimonial salts and pentamidine are associated with significant toxicity and failure rates. We examined the efficacy of KY62, a new, water-soluble, polyene antifungal, against cutaneous infection with Leishmania amazonensis and against visceral infection with Leishmania donovani in susceptible BALB/c mice. Mice were infected with L. amazonensis promastigotes in the ear pinna and in the tail and were treated with KY62 or amphotericin B. The cutaneous lesions showed a remarkable response to therapy with KY62 at a dose of 30 mg per kg of body weight per day. At this dose, the efficacy of KY62 was equivalent to or better than that of amphotericin B at 1 to 5 mg/kg/day. Mice infected intravenously with 107 L. donovani promastigotes and treated with KY62 showed a 4-log reduction in the parasite burden in the liver and spleen compared to untreated mice. These studies indicate potent activity of KY62 against experimental cutaneous leishmaniasis caused by L. amazoniensis and against experimental visceral leishmaniasis caused by L. donovani. 相似文献
12.
Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha. 总被引:18,自引:4,他引:18
下载免费PDF全文
![点击此处可从《The Journal of clinical investigation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Much of the clinically important pathology associated with IgE-dependent disorders is thought to reflect the actions of the blood-borne leukocytes recruited during these responses. To evaluate the extent to which mast cells are responsible for the leukocyte infiltration associated with IgE-dependent cutaneous reactions, we attempted to elicit these responses in normal mice, genetically mast cell-deficient W/Wv mice, and in W/Wv mice selectively repaired of their mast cell deficiency by the intradermal injection of cultured mast cells derived from the congenic normal (+/+) mice. We found that the tissue swelling associated with IgE-dependent passive cutaneous anaphylaxis reactions developed rapidly and diminished markedly from 2 to 4 h after antigen challenge, but remained detectable for at least 24 h after elicitation of the responses. Infiltration of leukocytes (predominantly neutrophils) also occurred at these sites, but reached maximal levels 6-12 h after antigen challenge, persisted at high levels for 24 h, and largely waned by 48 h. Virtually all of the tissue swelling and leukocyte infiltration associated with IgE-dependent cutaneous reactions was mast cell dependent. Intradermal injection of 40 U of recombinant murine TNF-alpha (rmTNF-alpha) elicited neutrophil infiltration similar in magnitude and kinetics to that observed after IgE-dependent mast cell degranulation. A rabbit anti-rmTNF-alpha (R anti-rmTNF-alpha) antiserum, which was able to inhibit 84% of the neutrophil infiltration observed after i.d. injection of rmTNF-alpha, inhibited IgE-, and mast cell-dependent leukocyte infiltration by 47 +/- 7% in three separate experiments. These findings indicate that TNF-alpha contributes to mast cell-dependent recruitment of leukocytes during IgE-dependent cutaneous late phase reactions, but suggest that other mast cell-associated mediators probably also contribute to this response. 相似文献
13.
A Miyake H Yamamoto Y Takebayashi H Imai K Honda 《The Journal of pharmacology and experimental therapeutics》1992,263(3):1302-1307
(+)-trans-4-(3-dodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4- hydroxyphenyl)chroman (YM-26567-1), a novel natural product isolated from the fruit of Horsfieldia amygdaline, dose-dependently inhibited group II phospholipase A2 (PLA2) prepared from rabbit platelet with an IC50 value of 6.7 microM (4.6-9.6 microM, n = 4). In contrast to irreversible PLA2 inhibitors such as manoalide and p-bromophenacyl bromide, the PLA2 inhibition of YM-26567-1 was independent of preincubation time. Lineweaver-Burk analysis revealed that YM-26567-1 behaved as a competitive inhibitor of rabbit platelet PLA2 with a Ki value of 1.6 +/- 0.3 microM (n = 5). Although YM-26567-1 also competitively inhibited group I PLA2 derived from porcine pancreas, the Ki value was approximately 10-fold greater for porcine pancreas than for rabbit platelet PLA2. In vivo, topical application of YM-26567-1 to the mouse ear inhibited 12-O-tetradecanoylphorbol-13-acetate (1 micrograms/ear)-induced mouse ear edema in a dose-dependent manner with a 50% effective dose of 28 micrograms/ear (13-63 micrograms/ear, n = 10/dose), but did not improve arachidonic acid (4 mg/ear)-induced mouse ear edema at 1 mg/ear. These results suggest that YM-26567-1 is a competitive PLA2 inhibitor showing a higher affinity for group II than group I PLA2, and that it may act as a potent anti-inflammatory compound through its direct inhibition of PLA2. 相似文献
14.
15.
James F Kachur Leslie J Askonas Doreen Villani-Price Nayereh Ghoreishi-Haack Suzanne Won-Kim Chi-Dean D Liang Mark A Russell Walter G Smith 《The Journal of pharmacology and experimental therapeutics》2002,300(2):583-587
Leukotriene (LT) A(4) hydrolase is a dual function enzyme that is essential for the conversion of LTA(4) to LTB(4) and also possesses an aminopeptidase activity. SC-57461A (3-[methyl[3-[4-phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl) is a potent inhibitor of human recombinant LTA(4) hydrolase (epoxide hydrolase and aminopeptidase activities, K(i) values = 23 and 27 nM, respectively) as well as calcium ionophore-induced LTB(4) production in human whole blood (IC(50) = 49 nM). In the present study, we investigated its action in several animal models. Oral activity was evident from the ability of the compound to inhibit mouse ex vivo calcium ionophore-stimulated blood LTB(4) production with ED(50) values at 1.0 and 3.0 h of 0.2 and 0.8 mg/kg, respectively. A single oral dose of 10 mg/kg SC-57461A blocked mouse ex vivo LTB(4) production 67% at 18 h and 44% at 24 h, suggesting a long pharmacodynamic half-life. In a rat model of ionophore-induced peritoneal eicosanoid production, SC-57461 inhibited LTB(4) production in a dose-dependent manner (ED(50) = 0.3-1 mg/kg) without affecting LTC(4) or 6-keto-prostaglandin F(1alpha) production. Oral pretreatment with SC-57461 in a rat reversed passive dermal Arthus model blocked LTB(4) production with an ED(90) value of 3 to 10 mg/kg, demonstrating good penetration of drug into skin. Plasma level of intact SC-57461 (3 h after oral gavage dosing with 3 mg/kg) was 0.4 microg/ml, which corresponds to >80% inhibition of dermal LTB(4) production. Oral or topical pretreatment with SC-57461A 1 h before challenge with arachidonic acid blocked ear edema in the mouse. SC-57461A is a competitive, selective, and orally active inhibitor of LTA(4) hydrolase in vivo, making it useful to explore the contribution of LTB(4) to a number of inflammatory diseases. 相似文献
16.
Beneficial effect of brewers' yeast extract on daily activity in a murine model of chronic fatigue syndrome 总被引:4,自引:0,他引:4
Takahashi T Yu F Zhu SJ Moriya J Sumino H Morimoto S Yamaguchi N Kanda T 《Evidence-based complementary and alternative medicine : eCAM》2006,3(1):109-115
The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-gamma and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses. 相似文献
17.
Lucas R Giannini C D'auria MV Payá M 《The Journal of pharmacology and experimental therapeutics》2003,304(3):1172-1180
The marine metabolite bolinaquinone is a novel inhibitor of secretory phospholipase A(2) (sPLA(2)), with a potency on the human synovial enzyme (group II) higher than that of manoalide. This activity on the sPLA(2) was confirmed in vivo in the 8-h zymosan rat air pouch on the secretory enzyme accumulation in the pouch exudate. Additionally, bolinaquinone decreased potently the synthesis and release of leukotriene B(4) (LTB(4)) in calcimycin (A23187)-stimulated human neutrophils as a consequence of the inhibition of 5-lipoxygenase activity, as well as PGE(2) and NO production on zymosan-stimulated mouse peritoneal macrophages. This compound exerted anti-inflammatory effects by topical and oral routes on the mouse ear edema induced by 12-O-tetradecanoylphorbolacetate, with ID(50) values of 76.7 microg/ear and 5.6 mg/kg, respectively, with a significant decrease in PGE(2), LTB(4), and tumor necrosis factor-alpha (TNF-alpha) levels being more effective than indomethacin. This effect was confirmed in the mouse paw carrageenan edema after oral administration. Moreover, bolinaquinone was able to reduce the inflammatory response of adjuvant arthritis by inhibiting PGE(2), NO, and TNF-alpha production in paw homogenates without affecting PGE(2) levels in the stomach. Additionally, bolinaquinone inhibited inducible nitric oxide synthase expression and reduced the degree of bone resorption, soft tissue swelling, and osteophyte formation. 相似文献
18.
Neutrophil-mediated changes in vascular permeability are inhibited by topical application of aspirin-triggered 15-epi-lipoxin A4 and novel lipoxin B4 stable analogues. 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《The Journal of clinical investigation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
T Takano C B Clish K Gronert N Petasis C N Serhan 《The Journal of clinical investigation》1998,101(4):819-826
Neutrophil (PMN) activation is critical in inflammation and reperfusion injury, suggesting that PMN-directed therapies may be of clinical use. Here, leukotriene B4 (LTB4)-induced PMN influx in ear skin was equivalent between 5-lipoxygenase knockout and wild-type mice. To explore actions of lipoxin (LX) in PMN-mediated tissue injury, we prepared several novel LX stable analogues, including analogues of LXA4 and aspirin-triggered 15-epi-LXA4 as well as LXB4, and examined their impact in PMN infiltration and vascular permeability. Each applied topically to mouse ears inhibited dramatically PMN-mediated increases in vascular permeability (IC50 range of 13-26 nmol) with a rank order of 15(R/S)-methyl-LXA4 > 16-para-fluoro-phenoxy-LXA4 approximately 5(S)-methyl-LXB4 >/= 16-phenoxy-LXA4 > 5(R)-methyl-LXB4. These LX mimetics were as potent as an LTB4 receptor antagonist, yet results from microphysiometry with mouse leukocytes indicated that they do not act as LTB4 receptor level antagonists. In addition, within 24 h of delivery, > 90% were cleared from ear biopsies. Neither IL-8, FMLP, C5a, LTD4, nor platelet-activating factor act topically to promote PMN influx. When applied with LTB4, PGE2 enhanced sharply both infiltration and vascular permeability, which were inhibited by a fluorinated stable analogue of aspirin-triggered LX. These results indicate that mimetics of LXs and aspirin-triggered 15-epi-LXA4 are topically active in this model and are potent inhibitors of both PMN infiltration and PMN-mediated vascular injury. 相似文献
19.
目的研究桑色素(morin)对二硝基氟苯诱导迟发型超敏反应的影响。方法建立二硝基氟苯(dinitroflu-orobenzene,DNFB)诱导迟发型超敏反应(delayed type hypersensitivity,DTH)模型,观察morin对DTH模型小鼠耳组织肿胀、炎性细胞浸润程度和胸腺指数、脾指数的影响,光学显微镜下观察小鼠耳廓组织学变化,噻唑兰(methyl thia-zolyl tetrazolium,MTT)法检测淋巴结细胞和脾脏淋巴细胞增殖情况。结果双耳称重的结果显示,morin(70mg/ml)处理组与DTH组具有显著的差异(P〈0.05),能明显抑制DNFB引起的炎症反应;耳廓局部组织学检测也表明,morin能够抑制DNFB诱导的DTH,明显减少淋巴细胞的浸润。morin能降低DTH小鼠胸腺指数和脾脏指数,抑制淋巴结淋巴细胞(P〈0.01)和脾脏淋巴细胞的增殖(P〈0.05)。结论 morin可显著抑制DTH小鼠耳组织肿胀和淋巴细胞浸润程度,降低胸腺和脾脏指数,抑制淋巴细胞的增殖可能是其作用机制之一。 相似文献
20.
The pharmacokinetics of intravenous netilmicin was studied in cystic fibrosis (CF) and non-CF patients who were closely matched according to age. The serum concentrations showed a moderately higher variance within the CF group. The serum half-life in CF patients was 1.37 h compared with 2.29 h in the non-CF subjects (P less than 0.05). The apparent distribution coefficients were 0.306 and 0.356 liters/kg in the CF and non-CF groups, respectively. The mean body clearance was 6.6 liters/h per 1.73 m2 in the CF group compared with 5.3 liters/h per m2 in the non-CF controls, but the difference was not significant. The mean renal clearance in CF patients was 4.7 liters/h per 1.73 m2. From a pharmacokinetic point of view, the dosage of netilmicin required may be the same in CF as in non-CF patients. 相似文献