共查询到20条相似文献,搜索用时 31 毫秒
1.
Y Yanagihara Y Tonami Y Soma M Ishizaki Y Miyamoto Y Yui T Shida 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1983,81(6):573-584
FUT-175 is a new anti-complemental drug which strongly inhibits complement-mediated allergic reactions in animals. It was reported that FUT-175 does not affect both antibody formation and host defense to bacterial infection in mice. The present study was undertaken to examine the effects of FUT-175 on various immunological reactions in humans. FUT-175 dose-dependently decreased the antigen-induced anaphylactic histamine release from leukocytes of atopic patients. However, i.d. treatment of FUT-175 neither inhibited antigen- or compound 48/80-induced immediate type skin reactions in atopic patients nor antigen-induced early, late or delayed type skin reactions in Candida-sensitive patients. FUT-175 also did not inhibit the PPD-mediated delayed type skin reaction in healthy subjects. FUT-175 at a dose of 10(-4)M but not at 10(-8) to 10(-5)M significantly decreased the proliferation of human atopic peripheral blood lymphocytes (PBL) caused by mite antigen, concanavalin A or pokeweed mitogen. 51Cr release from human PBL was slightly enhanced by FUT-175 at a dose range of 10(-6) to 10(-4)M. FUT-175 did not change the number of SIg receptors or C3 receptors on human B cells. FUT-175 hardly affected the nitroblue tetrazolium reduction test and Escherichia coli-mediated chemotaxis in human neutrophils. These results strongly suggest that FUT-175 does not affect immunological functions and host defense in humans. 相似文献
2.
M Oda M Ogihara T Sato M Kurumi M Iwaki 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1986,87(5):521-526
Effect of nafamostat mesilate (FUT-175), a serine protease inhibitor, having anti-inflammatory effects was studied on superoxide (O2-) production in rat polymorphonuclear leucocytes (PMN) and compared with those of other serine protease inhibitors and typical anti-inflammatory agents. 1) O2- productions in rat PMN stimulated with concanavalin A (Con A) and cytochalasin B (Cyt B) were too weak to observe. With NADH, however, strong O2- production was induced by Con A and Cyt B. 2) FUT-175 at 10(-6) and 10(-5) M inhibited O2- production in rat PMN induced by Con A and Cyt B with NADH in a concentration-dependent manner. 3) The serine protease inhibitor L-tosylamido-2-phenylethyl-chloromethyl ketone (TPCK) and soybean trypsin inhibitor (SBTI) inhibited O2- production at 10(-5) M and 10(-4) M, respectively, while aprotinin, chymostatin and leupeptin did not. 4) Neither indomethacin nor dexamethasone, typical anti-inflammatory agents, inhibited O2- production. Mepacrine, a phospholipase A2 inhibitor, strongly inhibited it. 5) O2- production in PMN prepared from the rat administered FUT-175, 200 mg/kg, p.o., was significantly decreased in comparison with that of the control rat. 6) FUT-175 had no effect on O2- production by hypoxanthine-xanthine oxidase. These results showed FUT-175 had a strong inhibitory effect on O2- production in rat PMN which other typical anti-inflammatory agents did not have. 相似文献
3.
Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats 总被引:2,自引:0,他引:2
M Iwaki Y Ino A Motoyoshi M Ozeki T Sato M Kurumi T Aoyama 《Japanese journal of pharmacology》1986,41(2):155-162
Effects of FUT-175 on the pancreatic enzymes in vitro and in vivo in the enterokinase-induced experimental acute pancreatitis were investigated, and they were compared with those of gabexate and aprotinin. In in vitro experiments, FUT-175 inhibited the pancreatic protease activities 10 to 100 times more potently than gabexate. Furthermore, FUT-175 inhibited the enterokinase activity. Unlike aprotinin, FUT-175 inhibited alpha 2-macroglobulin bound trypsin activity as well as free trypsin. In in vivo experiments, at doses of 0.5-50 micrograms/kg/min, FUT-175 suppressed the elevated protease activities in the experimental acute pancreatitis more potently than gabexate. Differently from the action of aprotinin, FUT-175 suppressed trypsin activities both in the pancreas and in the plasma to the same extent. Furthermore, FUT-175 reduced the mortality of rats in the experimental acute pancreatitis in a dose-dependent manner. These data strongly support that FUT-175 is clinically useful in the therapy of acute pancreatitis. 相似文献
4.
Pharmacological studies of FUT-175, nafamstat mesilate. III. Anti-inflammatory activities of FUT-175
M Iwaki M Oda M Ozeki Y Ino K Suzuki Y Koshiyama A Motoyoshi M Ogihara S Suzuki M Fujita 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1984,84(4):373-384
Anti-inflammatory effects of FUT-175 (nafamstat mesilate), a new synthetic serine protease inhibitor, on various types of experimental inflammation were investigated in vivo and in vitro, in comparison with non-steroidal anti-inflammatory drugs (NSAID). The in vivo studies showed that FUT-175 has the abilities to inhibit almost all types of inflammatory reactions employed in the present study. In particular, being evaluated on the basis of the effect of indomethacin, FUT-175 exhibited relatively higher potencies against some reactions such as zymosan-induced increase of vascular permeability, scald paw edema, zymosan-induced granuloma-pouch, the Arthus reaction and acetic acid-induced writhing in which the complement system or the kallikrein-kinin system are considered to play an important role. The in vitro studies showed that FUT-175 is quite different from NSAID, that is, FUT-175 had no effects on heat-induced erythrocyte-lysis and heat-induced denaturation of bovine serum albumin. FUT-175 also had no effect on chemotaxis of polymorphonuclear leucocytes, but inhibited the production of chemotactic factor by antigen-antibody reaction. These above results suggested that FUT-175 has a different mode of action from NSAID and that serine protease inhibiting activities of this compound might play an important role in its anti-inflammatory effect. 相似文献
5.
The effects of 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), a new antiallergic drug, on immunological reactions in mice and in humans were investigated. The mouse hemolysin formation against sheep erythrocytes was not suppressed by Sm 857 (10-100 mg/kg/d i.p., p.o.) for 3 days either before or after immunization. The formation of anti-dinitrophenyl (DNP) IgE antibodies in mice immunized with dinitrophenyl-conjugated ovalbumin (DNP-OA) and alum, was not suppressed by Sm 857 (10-100 mg/kg i.p., p.o.) for 3 days either before or after immunization, but the formation of anti-DNP IgG antibodies on 7 days after immunization was slightly suppressed in the group of mice treated i.p. with 100 mg/kg/d of Sm 857 for 3 days after immunization. On the other hand, both the proliferation of human peripheral blood lymphocytes (PBL) induced by concanavalin A, phytohemagglutinin-P, pokeweed mitogen (PWM), protein A (Pro A) and Cowan I, and the formation of IgM and IgG plaque forming cells by PBL stimulated with PWM or Pro A, were suppressed significantly only in the presence of Sm 857 (10(-4) g/ml). In addition, Sm 857 hardly affected the nitroblue tetrazolium reduction test, phagocytosis and chemotaxis in human neutrophils. 相似文献
6.
Y Koshiyama A Kobori M Ogihara Y Yokomoto K Ohtani K Shimamura M Iwaki 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1987,90(6):313-320
FUT-175 is a newly synthesized serine protease inhibitor. In the present study, we investigated the effects of FUT-175 on blood coagulation and experimental DIC. The effects on coagulation were examined in vitro by measuring the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) of rat plasma in the presence of FUT-175. FUT-175 exhibited remarkable anticoagulative effects to prolong APTT at a plasma concentration of 3 x 10(-7) M, PT at 1 x 10(-5) M and TT at 3 x 10(-5) M. The anticoagulative effect of FUT-175 at 1 x 10(-6) M on APTT was almost similar to that of heparin at 0.3 U/ml or that of gabexate mesilate at 1 x 10(-3) M. Experimental DIC was induced by a four-hr sustained intravenous infusion of endotoxin. FUT-175 was administered intraperitoneally prior to the injection of endotoxin or infused intravenously with endotoxin. As a result, the prolongation of APTT and PT, the decreases of fibrinogen level, platelet counts and complement level, and the increase of FDP were remarkably improved by FUT-175. Furthermore, glomerular fibrin deposits were reduced by the infusion of FUT-175. These results indicate that FUT-175, having a potent inhibitory effect on blood coagulation, is clinically applicable to therapy for DIC. 相似文献
7.
H Nagai H Yamada N Matsuura N Inagaki T Shimazawa A Koda 《Japanese journal of pharmacology》1984,35(1):55-60
Effect of 6-amidino-2-naphtyl-4-guanidinobenzoate dimethane sulfonate (FUT-175) on experimental glomerulonephritis in mice was studied. Employed models are nephrotoxic serum (NTS) nephritis in ddY or A/He mice, rabbit IgG (RGG) accelerated NTS nephritis in ddY mice and spontaneous nephritis in (NZB x NZW) F1 mice. The severity of nephritis was evaluated by measuring proteinuria and serological parameters and examining renal tissue by light microscopy. Therapy with FUT-175 clearly prevented the pathological changes of proteinuria and serological parameters in all four nephritis models. By contrast, treatment hardly affected histopathological changes of the kidney in any of the models. Cyclophosphamide used as a comparative drug showed more clearly remission of the onset and development of NTS nephritis and RGG accelerated NTS nephritis in ddY mice by means of the changes of urinary and selorogical parameters. These evidences suggest that FUT-175 shows beneficial effects on the nephritis in either normal or complement deficient mice. 相似文献
8.
It was reported that dialysate (BWD) separated from the aqueous extract of buckwheat was a haptenic substance capable of neutralizing IgE antibody on mast cells and that the activity was specific to non-dialysate (BWND)-induced hypersensitivity reaction. The effect of BWD on antibody formation was investigated in the present paper. In rats, anti-buckwheat IgE formation was slightly depressed by the administration of BWD, but both anti-DNP IgE and IgG formations in rats immunized with DNP-BWND were unaffected. In mice, anti-buckwheat IgE formation was suppressed by BWD administration. A good correlation was noted between a decrease of surface IgE population on B cells and that of IgE titer in serum. However, the helper function of T cells for adoptive anti-DNP IgE formation was little affected by BWD treatment. Lymphocyte transformation to BWND and other non-specific mitogens using spleen cells obtained from sensitized mice was inhibited in a dose-dependent fashion by the addition of BWD. However, lymphocyte transformation using spleen cells pretreated with BWD was not affected by other non-specific mitogens except for BWND and pokeweed mitogen. 相似文献
9.
It has already been reported that dialysate (BWD) separated from the aqueous extract of buckwheat is a haptenic substance capable of neutralizing specific IgE antibody both on mast cells and on B cells in some species. The present work represents a study carried out to determine the effect of BWD conjugated with T cell mitogen such as phyothemagglutinin-P (PHA) and concanavalin A (Con A) on IgE formation in mice. Anti-buckwheat IgE formation was little affected by the pretreatment of these conjugates given i.v. 3 days before the immunization, but was effectively suppressed by the pretreatment of BWD-PHA or BWD-Con A given i.p. together with incomplete Freund's adjuvant 2 weeks before the immunization. BWD-PHA induced a more potent suppression of IgE formation as compared with BWD-Con A, Con A or PHA. The transfer of T cells obtained from spleen cells primed with BWD-PHA, which responded with buckwheat and exerted a slight helper function for adoptive anti-DNP IgE formation to DNP-buckwheat, suppressed anti-buckwheat IgE formation in recipients with no effect on the anti-KLH IgE response. Our findings suggest that suppressor T cells specific to buckwheat are induced in spleen cells of mice treated with BWD-PHA. 相似文献
10.
1. The effects of FUT-175 on the development of adjuvant arthritis in rats were studied and compared with those of indomethacin. FUT-175 inhibited both primary and secondary paw lesions in the adjuvant arthritic rats when it was administered orally on a daily basis from the day before through 18th day after adjuvant injection. 2. In addition, FUT-175 inhibited the increase in hemolytic complement in adjuvant arthritic rats in a dose-dependent manner. 3. Indomethacin also showed an inhibitory effect on the development of arthritic lesion, but had no effect on the increase in hemolytic complement in the adjuvant arthritis in rats. 4. Furthermore, FUT-175 inhibited the activities of various proteases in vitro, and then strongly inhibited complement-mediated hemolysis via the classical and alternative pathways, while indomethacin had no effect on them. 5. These results suggest that the anti-inflammatory activity of FUT-175 may differ from indomethacin in the mechanisms of action and, at least in part, due to the anti-complement activity. 相似文献
11.
M Hisadome Y Nakamura T Okumoto K Ikegami 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1986,88(5):349-354
The production of hemolytic plaque forming cells (HPFC) in the spleen of BALB/c mice immunized with sheep red blood cells was significantly inhibited by carrageenan treatment (0.3 mg/kg, i.p.; on days -3 and -1). Cysteine ethylester hydrochloride (ethylcysteine) restored the inhibition of the HPFC production by carrageenan treatment in a dose-dependent manner (10-100 mg/kg, p.o.). Ia positive cells (antigen-presenting cells) increased in the spleen adherent cells (SAC) obtained from immunized mice, whereas they decreased in the SAC obtained from carrageenan-treated mice. An increase of Ia positive cells occurred in the SAC of carrageenan-treated mice given ethylcysteine. Ethylcysteine (10-100 mg/kg, p.o.; on days -2 and -1) prevented both the suppression of the HPFC production and the decrease of the number of thymus lymphocytes and peripheral leukocytes induced by cyclophosphamide treatment (30 mg/kg, i.p.; on days -1 and 0). Lyt 1.2 positive cells (helper T cells) decreased in the spleen T cells of cyclophosphamide-treated mice, but increased in the spleen T cells from cyclophosphamide-treated mice give ethylcysteine. On the other hand, Thy 1.2 negative cells (B cells) did not increase in the spleen cells of cyclophosphamide-treated mice with or without ethylcysteine. These results suggest that ethylcysteine restores the immune response in immunosuppressed mice through the functions of macrophages and/or helper T cells. 相似文献
12.
M Hisadome K Goto M Terasawa Y Kadobe C Abe Y Shiokawa 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1984,83(6):497-505
The production of spleen- and thymus-rosette forming cells (RFC) in BALB/c mice 4 days after immunization with 5 X 10(8) sheep red blood cells (SRBC) was inhibited by traxanox at doses of 10-30 mg/kg, p.o. This agent (100 mg/kg, p.o.) suppressed the 19S hemagglutinin titer and elevated the 7S hemagglutinin titer. The transfer of spleen-RFC of thymus-RFC into syngeneic recipient mice 4 days after immunization with SRBC increased the production of spleen hemolytic plaque forming cells (HPFC). This increase was abolished by the transfer of spleen-RFC obtained from mice treated with traxanox (30 mg/kg, p.o.), but not by the transfer of spleen-RFC treated with anti-Lyt 2.2 antiserum and complement. The viability of the spleen-RFC in mice treated with traxanox was decreased by treatment with anti-Lyt 2.2 antiserum and complement. Traxanox (3-30 mg/kg, p.o) significantly increased the inhibition of HPFC, spleen-RFC and thymus-RFC production by Concanavalin A at a dose of 50 micrograms/mouse. This agent (3-30 mg/kg, p.o) inhibited the production of HPFC, spleen-RFC and thymus-RFC in mice 4 days after the secondary immunization. These results suggest that traxanox may inhibit antibody production via the induction of Lyt 2.2 positive cells (suppressor T cells). 相似文献
13.
The in vitro and in vivo effects of the experimental immunomodulatory agent Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid) were studied in comparison with levamisole and indomethacin. Levamisole (4 mg/kg, i.v.) but not Wy-18,251 (less than or equal to 10 mg/kg, i.v.) enhanced carbon clearance rates in vivo in mice. Both Wy-18,251 and levamisole (100 mg/kg, p.o.) significantly suppressed the symptoms of experimental allergic encephalomyelitis (EAE) in rats injected with spinal cord emulsion, but neither were as effective as tilorone in this model. Wy-18,251 and levamisole (1-100 mg/kg, p.o.) suppressed the in vivo generation of plaque-forming cells (PFC) in mice immunized with sheep red blood cells while indomethacin (9 mg/kg, p.o.) enhanced PFC formation. All 3 agents (10(-5) - 10(-6) M) enhanced the in vitro ovalbumin (OA)-specific and Con A- or PHA-induced proliferative response and Con A-stimulated interleukin 2 (IL-2) synthesis of rat spleen cells. Furthermore, in vivo treatment of rats with 1-10 mg/kg (p.o.) of Wy-18,251 and levamisole but not indomethacin increased the subsequent in vitro mitogen or antigen (OA) responsiveness of spleen cells. None of the drugs (10(-5) - 10(-7) M) influenced the natural killer cell (NK) activity of rat spleen cells when incorporated directly into the 51Cr release NK assay. 相似文献
14.
N Matsuura H Mori H Nagai A Koda 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1992,100(6):485-493
We examined the effects of suplatast tosilate (IPD-1151T) on antibody formation in mice, and the following results were obtained: 1) IPD-1151T clearly increased the productions of IgM and IgG-hemolytic plaque forming cells (PFC) in mice immunized with sheep red blood cells (SRBC) when the agent was given p.o. for 5 days from the day of immunization. 2) IgM and IgG-PFC productions in old mice, 60 weeks of age, were clearly lower than those in adult mice, 10 weeks of age; and an oral administration of IPD-1151T significantly recovered the decayed PFC-production in the old mice. 3) IPD-1151T clearly suppressed the production of anti-dinitrophenyl (DNP)-IgE antibody in mice when the agent was given p.o. for 5 days from the day of immunization, whereas the agent did not affect anti-DNP-IgM and IgG antibody productions. 4) IPD-1151T did not affect the induction phase of the cellular immune reaction of picryl chloride-induced contact dermatitis and the SRBC-induced footpad reaction. Our present results suggest that IPD-1151T has a class-specific suppressive effect on the production of IgE antibody, but does not suppress the other immune responses. 相似文献
15.
H Murakami M Togawa S Takahashi N Kasahara J Yamamoto N Matsuura Y Koshiyama Y Ino M Oda 《Arzneimittel-Forschung》1990,40(12):1352-1358
The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis. 相似文献
16.
Kaoru Inouye Tomohiro Ito Hidekazu Fujimaki Yoshimasa Takahashi Toshitada Takemori Xiaoqing Pan Chiharu Tohyama Keiko Nohara 《Toxicological sciences》2003,74(2):315-324
In the humoral immune response to an invasion of foreign antigens, B cells differentiate into low-affinity antibody-forming cells (AFCs) that mainly secrete IgM or, through germinal center (GC) formation, into high-affinity AFCs that secrete IgG-class antibodies with a higher affinity for the antigen. Previous studies have established the suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on low-affinity antibody responses to antigens. However, whether and how TCDD affects the high-affinity antibody response to antigens has not yet been clarified. In this paper we investigate the effects of TCDD on GC formation, high-affinity AFC generation, and high-affinity antibody production in the primary humoral immune response. C57BL/6 mice were orally administered 0 or 20 microg/kg of TCDD and subsequently immunized with alum-precipitated ovalbumin (OVA) on day 0. Then the GC formation in the spleen and OVA-specific antibodies in the plasma, was evaluated until day 14 postimmunization. TCDD exposure reduced the production of OVA-specific IgG1 on days 10 and 14. GC formation in the spleen was also suppressed by TCDD exposure, and the suppression persisted from day 7 until day 14. In TCDD-administered mice, on day 7, cellular proliferation in the GCs was significantly suppressed, although apoptosis was not markedly affected. In order to measure high-affinity antibody and high-affinity AFCs, the mice were administered TCDD followed by immunization with alum-precipitated (4-hydroxy-3-nitrophenyl) acetyl linked to chicken gamma-globulin (NP-CG). The frequency of high-affinity NP-specific AFCs that bind to low-haptenated antigen was clearly shown to be reduced in the spleen on days 10 and 14. Furthermore, the high-affinity anti-NP IgG1 levels on days 10 and 14 postimmunization were significantly reduced by TCDD exposure. Taken together, the results of this paper demonstrate that TCDD exposure inhibits the generation of high-affinity AFCs and high-affinity antibody production during the primary humoral immune response and suggest that these alterations were caused by the suppression of antigen-responding B-cell proliferation induced by TCDD during GC formation. 相似文献
17.
Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum 总被引:14,自引:0,他引:14
The modulation of a polysaccharide-protein complex from Lycium barbarum (LBP3p) on the immune system in S180-bearing mice was investigated. The mice inoculated with S180 cell suspension were treated p.o. with LBP3p (5, 10 and 20 mg/kg) for 10 days. The effects of LBP3p on transplantable tumors and macrophage phagocytosis, quantitative hemolysis of sheep red blood cells (QHS), lymphocyte proliferation, the activity of cytotoxic T lymphocyte (CTL), interleukin-2 (IL-2) gene expression and lipid peroxidation were studied. LBP3p could significantly inhibit the growth of transplantable sarcoma S180 and increase macrophage phagocytosis, the form of antibody secreted by spleen cells, spleen lymphocyte proliferation, CTL activity, IL-2 mRNA expression level and reduce the lipid peroxidation in S180-bearing mice. The effect is not dose-dependent in a linear fashion. A total of 10 mg/kg dose is more effective than 5 and 20 mg/kg doses. This suggests that LBP3p at 10 mg/kg has a highly significant effect on tumor weight and improves the immune system. 相似文献
18.
The effect of disodium 4-chloro-2,2-iminodibenzoate (CCA) on IgE antibody response was examined in C3H/A and (BALB/c x C57BL/6J) F1 hybrid mice immunized with low doses of ovalbumin (OA) adsorbed on aluminium hydroxide gel. CCA administered orally at the doses of 5 and 50 mg/kg/day reduced IgE antibody production in these mice as determined by PCA test. High doses of CCA (100 mg/kg/day) given from day 7 before immunization of C57BL mice and during 1 week after immunization of mice with OA and Bordetella Pertussis Vaccine reduced the mortality of these mice subjected to anaphylactic shock on day 7 of immunization. CCA treatment was ineffective in anaphylactic shock of C57BL mice immunized with very high dose of OA, known to elicit little or no IgE antibody production but high IgG antibody response. The treatment of OA-immunized Guinea pigs with one oral dose of CCA (100 mg/kg) did not reduce mortality in protracted anaphylactic shock. Our results demonstrate that CCA inhibits IgE production as well as IgE mediated hypersensitivity reactions in mice. 相似文献
19.
N-Methanocarbathymidine [(N)-MCT] is a newly identified inhibitor of orthopoxvirus replication in cell culture and in mice. Limited published animal studies indicated the compound is effective by intraperitoneal (i.p.) route at 10-100 mg/(kg day). More extensive studies using different treatment regimens in intranasally infected mice were conducted in order to further explore the potential of this compound compared to cidofovir in treating vaccinia virus infections. (N)-MCT was given twice a day for 7 days, whereas cidofovir was administered once a day for 2 days, each starting 24h after virus exposure for most experiments. (N)-MCT was not toxic up to 1000 mg/(kg day) by the i.p. treatment route. Oral and i.p. treatment regimens with (N)-MCT were directly compared during a vaccinia virus (IHD strain) infection, indicating that the nucleoside has good oral bioavailability in mice. Treatments by i.p. route with (N)-MCT (100 mg/(kg day)) reduced lung, nasal, and brain virus titers during an IHD virus infection, but not nearly to the same extent as i.p. cidofovir (100 mg/(kg day)). Treatment with both compounds decreased liver, spleen, and kidney virus titers, as well as reduced lung consolidation scores and lung weights. Onset of treatment could be delayed by 2 days with (N)-MCT and by 3 days with cidofovir, providing significant survival benefit during the IHD virus infection. Against a vaccinia virus (WR strain) infection in mice, i.p. (N)-MCT treatment prevented death at 500 mg/(kg day), which was comparable in activity to i.p. cidofovir (100 mg/(kg day)). Significant reductions in tissue virus titers occurred with both treatment regimens. (N)-MCT could be further pursued for its potential to treat orthopoxvirus infections in humans. 相似文献
20.
L-Cysteine ethylester hydrochloride (ethylcysteine; 30 mg/kg, p.o.) increased the number of la-positive cells (antigen presenting cells) in spleen adherent cells (SAC) and that of Lyt 1.2-positive cells (helper T cells), but not that of Lyt 2.2-positive cells (suppressor T cells) of C57BL/6 mice immunized with sheep red blood cells. The production of hemolytic plaque forming cells (HPFC) in spleens of syngeneic recipient mice was enhanced by the transfer of SAC or spleen lymphocytes of the donor mice pretreated with ethylcysteine. This drug augmented phagocytosis of yeast particles by peritoneal macrophages of ICR mice at concentrations of 1-100 microM. In ex vivo experiments, this drug (30 mg/kg, p.o.) augmented the phagocytosis of yeast particles by mouse macrophages and showed a tendency to increase the macrophage number in the peritoneal cavity. Ethylcysteine (30 mg/kg, p.o.) significantly accelerated the decrease of viable E. coli number in the liver of normal mice 2 and 48 hr after challenge. Furthermore, this drug at the same dose restored the suppression of the decrease of E. coli number in the blood and liver of mice treated with cyclophosphamide (200 mg/kg, i.p.). These results suggest that ethylcysteine augments the functions of macrophages in vitro and ex vivo, and these enhancing effects may lead to the enhancement of host resistance to infections in compromised hosts. 相似文献