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Formation of GABOB from 2-hydroxyputrescine and its anticonvulsant effect.

To investigate the formation of gamma-amino-beta-hydroxybutyric acid from 2-hydroxyputrescine in mammalian organs, the radioactive diamine was synthesized and was injected into rats intraperitoneally or intraventricularly. After intraperitoneal injection, the radioactive amino acid was detected in various organs, but formation of the stereoisomer of the amino acid (gamma-amino-alpha-hydroxybutyric acid) was not demonstrated. Intraventricular injection of the radioactive diamine also resulted in the formation of gamma-amino-beta-hydroxybutyric acid in the rat brain. In vivo experiments using monoamine oxidase or diamine oxidase inhibitors suggested the participation of both enzymes in the formation of the amino acid from the diamine in rat organs other than the brain, where diamine oxidase appeared to play the major role. To investigate the anticonvulsant effect of 2-hydroxyputrescine, the threshold of pentylenetetrazol-induced generalized convulsions was measured in rats after the intraventricular injection of 2-hydroxyputrescine. Both R(-)- and S(+)-2-hydroxyputrescine had an anticonvulsant effect, with a greater elevation of the threshold being observed after injection of the R(-) form. Time course experiments suggested that this anticonvulsant effect depended on the formation of gamma-amino-beta-hydroxybutyric acid from 2-hydroxyputrescine in the rat brain. The anticonvulsant action of gamma-amino-beta-hydroxybutyric acid was also examined, and the stimulation of Cl- influx plus the inhibition of GABA uptake into brain membrane vesicles were indicated to be involved.

4-Aminobutyrate Transaminase↗

Lymphoid tissue responses to perfluorocarbon emulsion in mice.

The effects of either intraperitoneal or intravenous injection of low doses (5 or 10 ml/kg) of the proprietary emulsified perfluorocarbon-based blood substitute, Fluosol-DA 20%, on mouse lymphoid tissue and antibody production against sheep erythrocytes (SRBC) have been investigated. Mean liver weight was significantly increased and gut mesenteric lymph node (MLN) weights decreased in all animals injected with Fluosol-DA, irrespective of route of administration. In contrast, spleen weight decreased following intravenous injection of emulsion at 5 ml/kg. The mean plasma haemagglutination response to SRBC was significantly (P less than 0.01) increased in animals injected intraperitoneally with Fluosol at both doses but was similar to control in all other cases. These results show that lymphoid tissue responses to Fluosol-DA in mice are variable and that antibody production against intraperitoneally-injected SRBC is enhanced by prior injection of emulsion into the peritoneal cavity.

Animals↗

Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen-induced uveitis.

PURPOSE: Investigated the effect of N-3-aminomethylbenzylacetamidine (1400 W), a highly selective inhibitor of inducible nitric oxide synthase (iNOS), on the effector phase of EAU. METHODS: Sixteen Lewis rats were sensitized with bovine retinal S-antigen; ten of them injected subcutaneously with 1400 W (20 mg/kg) three times a day, from day 11 through day 13 following the injection of S-antigen. Five of the ten rats were also injected intraperitoneally with polyethylene-glycol-modified superoxide dismutase (SOD 1000 IU) twice a day from day 7 through day 13. Six rats received intraperitoneal and/or subcutaneous injections of normal saline from day 7 through day 13. The eyes were enucleated on day 14. The intensity of the inflammatory lesion was assessed by a histological score. The thickness of the choroidal and photoreceptor layers was measured. RESULTS: The histological score was higher in the 1400 W-treated rats (26 +/- 2.1) than in the saline- (20.5 +/- 8; p < 0.0001) or 1400 W/SOD-treated rats (20.5 +/- 4.9; p < 0.005). The choroid was thicker in the 1400 W-treated rats (60.7 +/- 16.8 microm) than in the saline- (19.2 +/- 9.4 microm, p < 0.0005) or the 1400 W/SOD-treated rats (29.6 +/- 19.3 microm, p < 0.05). The photoreceptor layer was thinner in the 1400 W-treated rats (8.4 +/- 32.1 microm) than in the saline- (40 +/- 26.7 microm; p < 0.05) or 1400 W/SOD-treated rats (60.8 +/- 38.1 microm; p < 0.05). CONCLUSIONS: The data suggests that 1400 W exacerbates choroidal inflammation and photoreceptor damage at the effector phase of S-antigen-induced uveitis. This implies that iNOS expressed in the outer retina may have a protective role in EAU.

Amidines↗

Enhanced thyroxine metabolism following cutaneous application of microscope immersion oil.

Microscope immersion oil, applied to the skin of rats or injected intraperitoneally, led to a substantial increase in the biliary excretion of intravenously injected 125-I-thyroxine (T4), elevated the bile: plasma 125-I ratio, enhanced the biliary clearance rate of plasma 125-I-T-4 and increased the proportion of biliary 125-I present as T-4-glucuronide. Immersion oil applied to the skin was at least as effective as injected intraperitoneally. Skin application also elevated bile flow, liver weight, thyroid 131-I uptake and Sephadex uptake of serum 125-I-triiodothyronine (indicating reduced binding of thyroid hormone to serum proteins) and depressed serum T-4 concentrations. These effects were similar to those previously observed after intraperitoneal injection of a polychlorinated biphenyl mixture.

Administration, Topical↗

A comparison of subcutaneous and intraperitoneal oxytetracycline injection methods for control of infectious disease in the rat.

After receiving once daily intraperitoneal (i.p.) or subcutaneous (s.c.) injections of oxytetracycline (15 mg/100 g bodyweight) for 7 days, laboratory rats had significantly different oxytetracycline serum levels depending on the method of injection. Regardless of injection method, the biological half-life of the antibiotic was 4.25 h and serum antibiotic levels never fell below therapeutic levels for certain rat pathogens during 24 h post-injection. Severe peritonitis and cellulitis were found in rats whether injected s.c. or i.p. and some animals lost bodyweight. It appeared that either injection method would be an effective treatment for certain infectious diseases of laboratory rats but tissue damage, probably from oxytetracycline's acidity, made both methods unattractive.

Animals↗

[Anti-endotoxin effect of lanthanum chloride in vivo: an experimental study of mice].

OBJECTIVE: Lanthanum is one of rare earth with extremely active chemical property and has been evidenced to possess antibacterial effect as well as the function of blocking calcium flux and regulating cellular immunity. Our previous studies showed that lanthanum could affect the biological activity of LPS and inhibit the activity in vitro. In this study, we explored the anti-LPS effects of lanthanum chloride in vivo so as to provide evidence in searching for new anti-endotoxic agents for the prevention and treatment of endotoxemia. METHODS: (1) 96 BALB/c mice were divided into 2 groups: experimental group including 84 mice injected intraperitoneally with 17.5 mg/kg, LD(50) dose, of LPS mixed with lanthanum chloride of the dosages of 1 mg/kg, 2 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, 40 mg/kg, and 80 mg/kg respectively; and control group including 12 mice injected intraperitoneally with 17.5 mg/kg of LPS. The mortality rates of different mice within 7 days were observed so as to observe the protective effect of lanthanum chloride. (2) 40 BALB/c mice were randomly divided into 2 group 2: experimental group injected intraperitoneally with lanthanum chloride of the dosages 10 mg/kg for 3 days and then injected with 1 LD(50) dosage of LPS 30 minutes after the last injection of lanthanum chloride of the dosages 10 mg/kg; and control group injected intraperitoneally with normal saline for 3 days and then with 1 LD(50) dosage of LPS 30 minutes after the last injection of normal saline. The mortality rates of different mice within 7 days were observed. (3) 40 BALB/c mice were randomly divided into 4 groups: LPS group, injected intraperitoneally with LPS of sublethal dosage (12.5 mg/kg), lanthanum chloride treatment group, injected intraperitoneally with LPS of sublethal dosage 1 hour after the venous injection of 10 mg/kg lanthanum chloride, lanthanum chloride control group, injected intravenously with 10 mg/kg lanthanum chloride, and NS control group, injected intraperitoneally with NS. Four hours after the intraperitoneal injection blood sample were collected to detect the plasma tumor necrosis factor-alpha (TNFalpha) and liver and thymus tissues were collected to examine the expression of TNFalpha mRNA and apoptosis of thymocytes by Rt-PCR and flow cytometry so as to observe the effects of lanthanum chloride on LPS-induced reaction in vivo. RESULTS: The mortality rates of the mice administrated with LD(50) dosage of LPS combined with 5, 10, and 20 mg/kg lanthanum chloride were 0, 0, and 8% respectively, all significantly lower than that of the control group (67%, all P < 0.01). The mortality rate of the LPS-challenged mice that were pretreated with 10 mg/kg of lanthanum chloride was 20%, significantly lower than that of the control group (55%, P < 0.05). (2) In the mice with endotoxemia that were pretreated with lanthanum chloride the plasma TNFalpha level was 0.44 +/- 0.22 ng/ml and the TNFalpha mRNA expression in liver was (3.93 +/- 0.62) x 10(5) copies/ micro g RNA, both significantly lower than those of the mice with endotoxemia without pretreatment of lanthanum chloride, 0.99 +/- 0.24 ng/ml and (1.9 +/- 0.33) x 10(7) copies/ micro g RNA (both P < 0.001). The percentage of DNA fragmentation of thymocytes in the mice challenged with LPS and pretreated with lanthanum chloride was 14.77% +/- 1.0%, significantly lower than that of the untreated mice (55.38% +/- 3.88%, P < 0.001), the percentage of hypodiploidy in thymocytes of the mice challenged with LPS was 15.56% +/- 0.59%, significantly higher than that of the lanthanum chloride treated mice (6.05% +/- 0.71%, P < 0.001). (3) Morphologic observation showed that pathological changes of the thymocytes and liver and lung tissues were remarkably milder in the lanthanum chloride-treated mice than in the mice challenged only by LPS. CONCLUSIONS: (1) Lanthanum chloride can bind LPS and reduce its toxicity, which shows protective effects on mice challenged by lethal dose LPS. (2) Lanthanum chloride can greatly decrease the secretion of TNFalpha and TNFalpha mRNA expression in the mice the secretion of TNFalpha and TNFalpha mRNA expression in the mice challenged with LPS. Furthermore, LPS-induced apoptosis of thymocyte and damage of liver and lungs are inhibited by lanthanum chloride.

Animals↗

Effect of berberine on myoelectric activity and transit of the small intestine in rats.

The motility of the small intestine in unanesthetized rats receiving berberine sulfate (0.2, 2.0, and 20.0 mg/kg i.p.) was investigated. Motility was determined by two methods: myoelectric activity was monitored with indwelling bipolar electrodes, and intestinal transit was measured by the movement of radiochromium (Na51CrO4). The 20.0-mg/kg dose caused a marked inhibition of spike activity for 21.8 +/- 7.0 min and disrupted activity fronts of the migrating myoelectric complex for 212.3 min. Berberine, 2.0 mg/kg i.p., disrupted migrating myoelectric complexes for 64.6 min but spike inhibition was not observed. Transit of the small intestine was significantly (p less than 0.001) delayed at 15 and 100 min after the highest dose of berberine. Naloxone blocked the spike inhibition noted with 20.0 mg/kg of berberine but failed to improve transit. Phentolamine blocked spike inhibition and was associated with a significantly earlier return of activity fronts of the migrating myoelectric complex. Animals pretreated with this antagonist tended toward a higher geometric center in transit studies than those injected with berberine alone. Berberine was also administered by various routes (intraperitoneal injection, intravenous injection, orogastric gavage, and intraluminal injection). An intraperitoneal injection was 10-fold more potent than an intravenous injection. Orogastric gavage and intraluminal administration of berberine did not alter intestinal motility. In summary, berberine sulfate significantly inhibits myoelectric activity and transit of the small intestine. This appears to be partially mediated by opioid and alpha-adrenergic receptors. The antidiarrheal properties of berberine may be mediated, at least in part, by its ability to delay small intestinal transit.

Administration, Oral↗

Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline.

Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.

Acetylmuramyl-Alanyl-Isoglutamine↗

Production of monoclonal antibodies to squamous cell carcinoma antigens.

For therapeutic or diagnostic use of monoclonal antibodies in clinical oncology, high-affinity IgG antibodies to tumor-associated antigens have to be generated. In order to find out by what immunization schedule the chance to generate such antibodies is increased, we evaluated three different immunization protocols with and without attempts to induce tolerance to common tissue antigens. Mice were immunized either (1) by repeated intraperitoneal injections, (2) by a single intrasplenic injection, or (3) by an intraperitoneal injection followed by an intrasplenic booster. Whereas a single intrasplenic immunization resulted in low-affinity antibodies to tumor-associated antigen, high-affinity antibodies were generated with the other two protocols, although at a lower frequency. No benefit was seen from tolerance induction. The intraperitoneal/intrasplenic protocol was found to be superior over the other protocols because of minimal antigen dose and immunization time, as well as a higher frequency of hybridoma formation.

Animals↗

Mortality rate and bacteremia, endotoxin, and endothelin-1 levels in antibiotic therapy for E. coli septic peritonitis.

In order to study the mortality rate and bacteremia, plasma endotoxin, and plasma endothelin-1 levels in antibiotic therapy for E. coli peritonitis, blood samples were obtained from rats given intraperitoneal injections of latamoxef or placebo. Intraperitoneal injections of latamoxef improved the prognosis of peritonitis rats. Two h after treatment, bacteremia levels were noticeably higher in rats treated with placebo than in rats treated with latamoxef, but the latamoxef-treated group manifested a significant elevation of plasma endotoxin and endothelin-1 levels compared to the placebo-treated group. The results of this study demonstrate that treating E. coli septic peritonitis with selected antibiotics induces increased plasma endotoxin levels, which are associated with elevation of plasma endothelin-1 levels.

Animals↗

Effect on fetal mouse development of exposure to MR imaging and gadopentetate dimeglumine.

Pregnant mice were exposed to one of five regimens at 9.5 days of gestation: no treatment (group 1), intraperitoneal injection of normal saline (group 2), intraperitoneal injection of gadopentetate dimeglumine (group 3), intraperitoneal injection of gadopentetate dimeglumine and magnetic resonance (MR) exposure (group 4), and MR exposure alone (group 5). At 18 days of gestation, the mice were sacrificed and fetuses were removed and examined for the following end points: litter size, number alive or dead, fetal weight, extremity morphology, eye and ear development, and appearance of the head. A total of 739 fetuses were analyzed: group 1 (n = 161), group 2 (n = 149), group 3 (n = 142), group 4 (n = 136), and group 5 (n = 151). The only statistically significant difference was a lower mean fetal weight in the saline-injection group compared with the control group. The results show that MR exposure with and without gadopentetate dimeglumine had no adverse effect on the end points analyzed.

Analysis of Variance↗

Systemic but not central administration of tumor necrosis factor-alpha attenuates LPS-induced fever in rats.

The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 microgram) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 microliter of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 micrograms/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 micrograms/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 microgram/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 +/- 0.12 degrees C in rats injected with hrTNF and LPS vs. 38.73 +/- 0.04 degrees C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.

Analgesics, Non-Narcotic↗

The primary immune response in mice. I. The enhancement and suppression of hemolysin production by a bacterial endotoxin.

The manner in which a single injection of S. typhosa endotoxin effects the primary hemolysin response to sheep erythrocytes in the mouse has been shown to depend on the dosage, route, and time of administration of the endotoxin, as well as on the route employed for the injection of antigen. The normal production of antibody, following an intravenous or an intraperitoneal injection of red blood cells, is suppressed if the bacterial lipopolysaccharide is given before and by the same route as the antigen. The response to an intraperitoneal injection of sheep red cells is also inhibited if preceded by an intravenous injection of endotoxin. By contrast, hemolysin formation to intravenous antigen is enhanced considerably by a previous intraperitoneal injection of endotoxin, and the response both to intravenous and to intraperitoneal injections of the antigen increases if the endotoxin is given by the same route either simultaneously or shortly after the foreign red cells. These findings are discussed in regard to the physiological action of bacterial endotoxins and the early events in antibody formation.

Adjuvants, Immunologic↗

Effect of liposomal interleukin-2 on ascites-forming rat hepatoma.

Interleukin-2 was entrapped in liposomes (Lip-IL-2) and injected into rats. The intraperitoneal injection of Lip-IL-2 into rats bearing an ascites-forming rat hepatoma (AH-66) significantly increased the survival time when compared with rats administered free IL-2 or saline-containing liposomes. The number of peritoneal exudate cells (PEC) increased markedly after intraperitoneal injection of Lip-IL-2 and consisted mainly of macrophages. The level of tumor necrosis factor alpha (TNF-alpha) and the intensity of free radicals increased in the ascites at 48 hrs after Lip-IL-2 administration, whereas TNF-alpha was not detected and the intensity of free radicals did not increase after free IL-2 administration. Our findings suggested that entrapment of IL-2 into liposomes enhanced its potential for cancer therapy, presumably by activating macrophages to produce TNF-alpha and free radicals.

Animals↗

Induction of hepatic metallothionein by intraperitoneal metal injection: an associated inflammatory response.

The nature of hepatic metallothionein (MT) induction by several metals and its relationship to an inflammatory response was studied in chicks. Intraperitoneal (ip) injection of chromium (Cr), managanese, and iron (Fe) caused a much greater increase in hepatic MT (10.2-, 9.0-, and 6.8-fold) compared with cobalt and nickel (2.5- and 2.9-fold); thus not all transition metals are effective. Cr3+ caused markedly greater hepatic MT accumulation than Cr6+, suggesting that the ionic nature of the metal is an important factor. Small organic complexes of Fe (ferrous gluconate or lactate, 6.2-fold) caused significantly greater accumulation of hepatic MT than ferric dextran (1.4-fold), a large organic aggregate. In vitro data from chick hepatocytes and/or fibroblasts clearly indicated that Fe does not effect the induction of MT directly. The role of inflammation, as measured by recruitment of peritoneal exudate cells (PEC), was examined. Endotoxin (LPS), Sephadex (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S = Fe greater than LPS much greater than control). The percentage of heterophils but not macrophages was significantly correlated with the accumulation and induction of hepatic MT. In a similar experiment with Cr, we demonstrated that Cr3+ but not Cr6+ stimulated MT messenger RNA accumulation and concomitant hetereophil infiltration at 3 h after injection. Our results indicate that the induction of hepatic MT by the parenteral administration of a number of metals is dependent on the chemical nature of the metal and is associated with an inflammatory response.

Animals↗

Role of dopaminergic and GABAergic mechanisms in discrete brain areas in phencyclidine-induced locomotor stimulation and turning behavior.

This study was designed to test whether phencyclidine (PCP)-induced turning behavior and locomotor stimulation result from the action of this drug on functionally different neuronal systems and different sites of the brain. PCP produced turning behavior towards the drug injection side with unilateral injection of PCP (50-100 micrograms) into the globus pallidus, but not the nucleus accumbens and the caudate nucleus. This turning behavior was strongly attenuated by a gamma-aminobutyric acid (GABA) antagonist, bicuculline, and by pimozide which reduces dopaminergic transmission in non-injection sites. Turning behavior induced by intraperitoneal injection of PCP (7.5 mg/kg) was enhanced by a GABA agonist, baclofen, and attenuated by GABA antagonists (bicuculline, picrotoxin). On the other hand, PCP produced significant locomotor stimulation, sniffing, rearing and forward locomotion with unilateral injection of 25-100 micrograms into the nucleus accumbens and the caudate nucleus. These behaviors were strongly antagonized by intraperitoneal injection of pimozide. The locomotor stimulation induced by intraperitoneal injection of PCP (5 mg/kg) was markedly enhanced by a small dose of methamphetamine and, by contrast, attenuated by reserpine, 6-hydroxydopamine, haloperidol, pimozide and a low dose of apomorphine which inhibits the release of dopamine by the stimulation of presynaptic receptors. These results suggest that PCP-induced turning behavior may be produced through stimulation of GABAergic transmission in the globus pallidus, although PCP-induced locomotor stimulation, sniffing, rearing and forward locomotion may be produced by increasing dopaminergic transmission in the nucleus accumbens and the caudate nucleus.

Animals↗

Preventive effect of recombinant human lactoferrin on lipopolysaccharide-induced preterm delivery in mice.

BACKGROUND: In order to investigate whether recombinant human lactoferrin (rh-LF) has the same effect as bovine LF (b-LF) for the prevention of preterm delivery, we conducted the following animal studies. METHODS: Female C3H/HeNCrj mice were pair-mated with male Crj:B6D2F1 mice. As a model of preterm delivery, on day 15 of gestation, a 50 microg/kg intraperitoneal injection of lipopolysaccharide (LPS) was administered twice with a 3-hr interval between injections (14:00 and 17:00 hours). At 1 hr prior to each LPS injection (13:00 and 16:00 hours), an intraperitoneal injection of saline, b-LF, or rh-LF (1 mg/body) was administered. In non-LPS-treated controls, an intraperitoneal injection of saline was administered four times (13:00, 14:00, 16:00, and 17:00 hours). We measured body weight and recorded delivery time. To measure plasma levels of interleukin-6 (IL-6), other pregnant mice, in which the same preparation as mentioned above had been done, were killed 6 h after the second LPS injection and blood samples were obtained. RESULTS: Delivery occurred in preterm (16.2 +/- 0.4 days of gestation) in all LPS-treated mice not administered LF. LF significantly prolonged gestation of LPS-treated mice: LPS + b-LF, 17.8 +/- 0.3 days; LPS + rh-LF, 18.2 +/- 1.3 days (p < 0.05). LF (1 mg/body) significantly suppressed plasma IL-6 in LPS-treated mice: LPS + b-LF, 1060 +/- 154; LPS + rh-LF, 244.2 +/- 59.4; and LPS without LF, 1628 +/- 115 pg/ml (p < 0.05). CONCLUSIONS: rh-LF has an effect of prolongation of gestation in LPS-induced preterm delivery in mice, suppressing LPS-induced plasma IL-6 augmentation.

Animals↗

[Suppressive effect of methylprednisolone on bovine serum albumin nephritis in mice].

Experiments were undertaken to study whether progressive processes of bovine serum albumin (BSA) nephritis in C57BL/B10-BR mice could be prevented by the treatment with methylprednisolone (MPSL), a glucocorticoid. Crescentic glomerulonephritis could be induced in 22 mice with high 95 per cent reproducibility by preimmunization of 0.2 mg of BSA four times every 2 weeks, followed by daily intraperitoneal injections of 50 mg/kg of BSA for 4 weeks (group IV, a control). In groups of 8 mice each, intraperitoneal injection of 50 mg/kg of MPSL was initiated 3 days before preimmunization (group I), before daily intraperitoneal injection of BSA (group II), and after daily intraperitoneal injection of BSA (group II), and after daily intraperitoneal injection of BSA (group III). In each group, the treatment was continued until the final day of the experiment. In group I, anti-BSA antibody titers, the levels of circulating immune complexes (CIC) and urinary protein was significantly suppressed in comparison with those in group IV. Histologically, diffuse intra- and extra-capillary proliferation observed in group IV was apparently inhibited. In group II and III, urinary protein and intra-/extracapillary proliferation were significantly diminished compared with those of group IV in spite of minor or no decrease in antibody titers and the CIC levels. These results suggest that MPSL has a suppressive effect on the progressive processes of immune complex mediated glomerulonephritis through both its immunosuppressive and antiinflammatory actions, especially when used in the early stage of immune reaction.

Animals↗