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PubMed1975

Experimental aspergillosis in rats infected via intraperitoneal and subcutaneous routes.

Normal adult rats infected via the subcutaneous (s.c.) route with viable spores of Aspergillus fumigatus develop serum antibodies, measured by passive haemagglutination and passive cutaneous anaphylaxis (PCA), to extracts of the fungus. No significant histological abnormality was detected but s.c. inoculation in cortisone-treated animals induced the formation of granulomas frequently found in lymph nodes including those of the mesentery and paratracheal group. These granulomas were associated with the presence of both spores and fungal hyphae. Intraperitoneal inoculation of A. fumigatus spores occasionally produced lesions containing hyphae in the liver, spleen and mesenteric lymph nodes. Lesions were more frequent and extensive in cortisone-treated rats where again they were most prominent in the mesenteric lymph nodes. None of the regimes produced fatal hyphal aspergillosis. Both normal and cortisone-treated rats developed serum agglutinins but not reagins following intraperitoneal injection of spores.

Animals↗
PubMed2000

Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice.

Interleukin-1 (IL-1) mediates symptoms of sickness during the host response to infection. IL-1 exerts its effects via several subtypes of receptors. To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL-1RI-/- mice were resistant to the sickness-inducing effects of IL-1beta administered intraperitoneally (2 microg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 microg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL-1RI-/- mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL-1, since lipopolysaccharide-induced expression of brain IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 transcripts were identical in IL-1RI-/- and control mice when measured by semiquantitative reverse-transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF-alpha action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 microg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 microg/mouse) on behaviour in IL-1RI-/- but not in control mice. Since IL-1RI-/- mice were not more sensitive to intracerebroventricularly TNF-alpha (50 ng) than control mice, these results indicate that IL-1RI mediates the sickness effect of IL-1 and that TNF-alpha simply replaces IL-1 when this last cytokine is deficient.

Animals↗
PubMed2002

Evaluation of potential antigenicity of active-site-inhibited recombinant human FVIIa (FFR-rFVIIa) in an immune-tolerant rat model.

Recombinant human FVIIa (rFVIIa) was inactivated by coupling Phe-Phe-Arg-CK- (FFR) covalently to the active site of the enzyme. To test the chemically-modified human protein for potential antigenicity prior to clinical trial an immune-tolerant rat model was established. Intraperitoneal injection of the parent compound, human rFVIIa, within 30 h after birth, followed by repeated subcutaneous challenge with rFVIIa in Freunds incomplete adjuvant resulted in 79% non-responding rats at day 32. Monthly subcutaneous challenge showed that the induced tolerance was stable over the 3 months study period in 80% of the rats. The clinically relevant route, intravenous administration, was used for evaluating the potential antigenicity of FFR-rFVIIa. Repeated intravenous administration of different dosages of FFR-rFVIIa did not break tolerance, indicating that FFR-rFVIIa might not be antigenic, for a limited number of intravenous administrations in a clinical setting.

Amino Acid Chloromethyl Ketones↗
PubMed1992

In utero transplantation of stem cells in humans: technical aspects and clinical experience during pregnancy.

Four fetal patients have received fetal liver cell transplants in utero, at the fertilization ages of 12-28 weeks. Depending on the age, intraperitoneal injection or intravenous infusion into the umbilical vein was used, under ultrasonic guidance. In three of the four cases, engraftment has been obtained and has resulted in cure or significant improvement of the inherited disease.

Blood Component Transfusion↗
PubMed1992

[Effects of neuropeptide Y on rat body temperature in normal conditions and after ethanol administration].

It was shown that intracerebroventricular (icv) administration of 2 micrograms neuropeptide Y (NPY) increased the rectal temperature in rats 2.5 hours postinjection. During 5 days we analysed dynamics of the effect of NPY on alcohol-induced hypothermia in this particular interval. 2 micrograms of NPY were given daily 30 min prior to 25% solution of ethanol (3 g/kg weight rat) intraperitoneal injection. It was found that NPY can prevent the attenuation of alcohol hypothermia on the 3-d and 4-th injection day. It was supposed that the inhibitory effect of NPY on the development of alcohol tolerance may be due to the capacity of NPY to increase food behavior. So it's known that activation of other competitor motivation may inhibit the development of alcoholism.

Alcoholism↗
PubMed2004

[Wide range of the use of natural lipases and esterases to inhibit Mycobacterium tuberculosis].

Lipases and/or esterases (hereinafter referred to as esterases) isolated from the wax moth (Galleria mellonella) were found to have a bacteriological action on Mycobacterium tuberculosis (MBT) H37Rv. Different types of raw esterase preparations (REP) were incubated with MBT at 37 degrees C for 18 hours, the incubate was seeded on the Finn-II solid medium or intraperitoneally injected into guinea pigs in a single dose of 100,000,000 bacteria. There was no growth of MBT in the medium within 8 weeks, some variants of REP causing a destruction of the medium for 3-7 days. This "toxic" effect on the lipid-containing Finn-II medium could be lowered by the simplest techniques for purifying esterases. In the experimental guinea pigs, a tuberculous process substantially regressed: autopsy of control animals at interval of 3-6 weeks after inoculation with native MBT showed the typical picture of progressive generalized tuberculosis; at the same time a visible pathology was not noted in the animals contaminated with MBT incubated with esterases. At week 7, control guinea pigs died; the onset of a tuberculous process was observed in experimental guinea pigs at week 8. An attempt to reveal the therapeutical effect of REP on guinea pigs with tuberculosis in a direct experiment failed. At the same time, there was a low toxicity of REP (in the used doses) for guinea pigs and B10.A(4R) mice. Based on their own findings and some data available in the literature, the authors have arrived at the following provisory conclusions: the studied REPs contain mammalian lysosomal lipase-type enzymes that determine the bacteriostatic and, perhaps, bacteriolytic effect of REP shown on MBT in vitro; there is evidence for promises of continued detailed studies of natural esterases for searching new antituberculous agents. A program of investigations of the studied and other natural esterases has been developed by taking into account the authors' developments and know-how. The study may be regarded as part of global unselected screening of biological and other materials for detecting new promising sources of drugs.

Animals↗
PubMed1992

Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparison with interleukin-1.

Administration of either endotoxin (lipopolysaccharide, LPS) or interleukin-1 (IL-1) activates the hypothalamic-pituitary-adrenal axis and cerebral catecholamine systems. Because LPS can stimulate IL-1 production in vivo, it is possible that the effects of LPS are mediated by IL-1. This hypothesis was evaluated by comparing the neurochemical and corticosterone responses to i.p. LPS and IL-1. In addition, the possibility that LPS acts by penetrating the brain was examined by comparing the neurochemical responses to i.p. and i.c.v. administration. Intraperitoneal injection of LPS increased mouse brain concentrations of the norepinephrine catabolite, 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG), the dopamine catabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), and the 5-hydroxytryptamine catabolite, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan in all brain regions examined. By contrast, i.p. IL-1 alpha and IL-1 beta increased cerebral concentrations of MHPG, 5-HIAA and tryptophan, but not DOPAC. The MHPG responses to IL-1 were substantially greater in hypothalamus than in other brain regions, whereas those to LPS were less regionally specific. The minimum effective doses of LPS and IL-1 were around 1 microgram and 10 ng, respectively. After i.p. LPS, plasma concentrations of corticosterone, DOPAC and MHPG peaked around 2 hr, whereas peak concentrations of tryptophan and 5-HIAA occurred around 8 hr. Intracerebroventricular LPS also elevated plasma corticosterone and cerebral concentrations of MHPG and 5-HIAA, but DOPAC was unchanged. LPS was not substantially more potent i.c.v. than i.p.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

[Inhibition of carrageenan edema by carrageenan itself].

The influence of two kinin forming agents: iota carrageenan and ellagic acid, on the paw oedema induced by 48/80, an amino-liberator, or by carrageenan iota, has been studied, in the Rat. Ellagic acid and carrageenan, by intraperitoneal injection, reduce the paw oedema induced respectively by 48/80 and carrageenan itself. This inhibition depends on a non-specific "counter-irritation" and not on kininogen stores depletion. Ellagic acid, by intravenous injection, diminishes the oedema induced by carrageenan; swelling due to 48/80, is not affected. So kininogen activation plays some role in the inflammatory processes induced by iota carrageenan. Carrageenan by intravenous injection, suppresses his own inflammatory action but does not influence at all the similar action of 48/80. The anti-inflammatory effect of carrageenan does not exclusively depend on kininogen stores depletion.

Animals↗
PubMed2005

Response of different organs of immune system of mice upon administration bacterial CpG DNA.

UNLABELLED: CpG DNA are potent immunostimulator and currently being tested as adjuvant in immunotherapy of various diseases. THE AIM of this study was to investigate the effects of a single dose of bacterial CpG DNA challenge on response of murine immune system organs and on a zeta-potential of different lymphoid organ cells and peritoneal macrophages in normal and tumor-bearing mice. METHODS: Indexes and cellularity of immune organs of mice were evaluated. Z-potential was measured by cellular electrophoresis. RESULTS: Subcutaneous administration of CpG DNA induced local transitory hyperplasia of lymph nodes, moderate increase of splenic index and total spleen cellularity, whereas intraperitoneal injection of CpG DNA caused full-blown spleen enlargement and increase of splenocyte content, and also mice showed transitory aseptic peritonitis. Response of thymus on challenge of CpG DNA was bi-phase: initial phase - response on antigen as stimulus, and late proliferative phase. It was noted that tumor growth does not affect zeta-potential in peritoneal macrophages and mononuclear lymphocytes, but causes increase of zeta-potential on thymocytes and decreases it in lymphocytes from lymph nodes. Furthermore, single administration of CpG DNA normalizes of thymocytes and lymph nodes lymphocytes zeta-potential and increases it in peritoneal macrophages and mononuclear lymphocytes. CONCLUSION: The findings demonstrate a close correlation between the hyperplasia of lymphoid follicles induced by challenge of CpG DNA and increase of their cellularity. Observed Z-potential alterations of immune system cells after CpG DNA immunization evidence on more significant polyanion accumulation on the surface of splenic macrophages and mononuclear cells.

Adjuvants, Immunologic↗
PubMedDate not supplied

Effect of AgK114 on picryl chloride-induced chronic contact hypersensitivity responses.

BACKGROUND: Mouse AgK114 (a glycosylphosphatidylinositol (GPI) anchored membrane-associated protein) expression is found in somatotrophs of the pituitary gland in correlation with the expression of growth hormone. In this study, the effects of AgK114 on the systemic immune response were examined in contact hypersensitivity (CHS) model mice. MATERIALS AND METHODS: AgK114 was intraperitoneally injected into BALB/c mice that were sensitized and challenged with picryl chloride (PiCl). Serum IgE levels and the antigen-specific cytokine production by lymph node (LN) cells were examined. RESULTS: The serum IgE levels in the CHS mice treated with 10 microg/head of AgK114 during the repeated challenge with PiCl were significantly decreased compared with those of the control mice. Moreover, IL-4 production by LN cells in response to 2,4,6-trinitrobenzene-sulfonic acid sodium salt-treated splenocytes was decreased in the AgK114-treated CHS mice compared with that of the control mice. CONCLUSION: Our results suggest that systemic administration of AgK114 exerted immunoregulatory functions on the allergic responses, resulting in the inhibition of IgE production.

Animals↗
PubMed2006

[Effect of amber acid on the kidney function in gentamycin-induced nephropathy in white rats].

The amber acid neutralized by 10 % solution of NaOH in a concentration of 250 mmoL/L was administered subcutaneously simultaneously with intraperitonal injection of gentamycin in a doze of 10 mg/kg(bw) once a day during 7 days to the ten nonlinear white male rats, weight 100-120 g exposed to the water-induced diuresis. In these experiments the positive action of an amber acid as energy substratum on some renal function tests was shown: improvement of reabsorbtion in proximal tubules, proved by proteinuria decrease, subsequent normalization of glomerular filtrations followed by uremia reduction and diminishing of other signs of acute renal failure.

Acute Kidney Injury↗
PubMed1988

New xenograft model for assessing experimental therapy of central nervous system tumors: human glioblastoma in the intrathecal compartment of the nude mouse.

Ten congenitally athymic "nude" mice and 10 immunocompetent mice underwent intrathecal inoculation with a human glioblastoma cell line (U87MG) via percutaneous lumbar puncture (5 x 10(5) cells/animal). All of the nude mice developed paraplegia with or without incontinence at 2 weeks and routinely died of inanition 3 weeks postimplantation. Histological examination confirmed extensive proliferation of neoplastic cells within the intrathecal space. A second group of animals was inoculated with 5 x 10(4) cells/animal: 20 nude mice, 10 cyclosporine A-immunosuppressed animals, and 10 immunocompetent control mice. The 20 mice were further divided into four subsets. Subset A did not receive chemotherapy, Subset B received 200 mg of carmustine (BCNU) per m2 by intraperitoneal injection, Subset C received a single dose of 4 mg of methotrexate (MTX) per m2 by intrathecal injection 4 hours after tumor inoculation, and Subset D received 12 mg of intrathecal MTX per m2. Decreasing the concentration of cells per animal by 1 log doubled the time interval required for the development of paralysis and incontinence to 4 weeks. Treatment with intrathecal MTX at a dose of 4 mg/m2 extended the symptom-free period by an additional week (to 5 weeks postinoculation), and a dose of 12 mg/m2 allowed an average of 6 weeks before the onset of neurological impairment. The xenografts did not grow in the immunocompetent control mice, the BCNU-treated group, or the cyclosporine A-immunosuppressed animals. An intrathecal xenograft model of central nervous system malignancies allows a novel approach to the evaluation of experimental chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Tumor development in lung of ddY mice following transplacental exposure to 1-ethyl-1-nitrosourea.

Transplacental induction of lung tumor by 1-ethyl-1-nitrosourea (ENU) was studied in pregnant ddY mice which were given a single intraperitoneal injection of 58.5 mg/kg of ENU in water between day 13 and 19 of gestation. Within 4 approximately 6 weeks after birth, pulmonary tumor nodules were found in all offsprings exposed to ENU, and they were histopathologically adenoma. Number of tumor nodules could be counted under the stereomicroscope from approximately day 40 after birth. The size of tumor increased with the lapse of time but the number of tumor nodules did not increase markedly. Weekly injections of urethan or ENU into mice pretreated with ENU in their fetal age enhanced the number of pulmonary adenoma. The development of other tumor was not seen except a few cases of lymphoma. Tumor development in the lung by injection of ENU in ddY mice during gestation is reproducible, relatively simple, and rapid. Therefore, it is considered that this may be a useful method for screening of antitumor agent.

Adenoma↗
PubMed1981

Immune response of rabbits immunized with proteolytic enzymes of B. subtilis.

This investigation was carried out to determine antigenic potency of the proteolytic enzymes: Alcalase, Maxatase and crystalline subtilisin type VII. To proof the antigenicity of these enzymes the precipitating antibodies in serum of immunized rabbits were determined. The titre of precipitating antibodies depended on the mode of immunization, preparation and concentration of antigens. The authors compare the effect of the immunization by subcutaneous and intraperitoneal injections of proteolytic enzymes on the production of serum precipitins in rabbits.

Animals↗
PubMed1977

Origin of ciliated alveolar epithelial cells in bleomycin-induced lung injury.

Bleomycin is known to induce diffuse pulmonary fibrosis and epithelial metaplasia. The reaction of the alveolar epithelium following a single intravenous or multiple intraperitoneal injections of bleomycin to mice is now examined in a combined morphologic and cytodynamic study. Necrosis of Type 1 cells was observed, followed by proliferation of Type 2 cells, a common reparative process. The proliferated cells transformed to a variety of epithelial forms, including ciliated cells and cells with morphologic features intermediate between alveolar and bronchiolar epithelium. No evidence of cell injury or increased cell division was found in the bronchial epithelium. It is concluded that the metaplastic ciliated epithelial cells are produced by an abnormal reparative process in the alveolar epithelium. The results suggest that, whereas the "resting" Type 2 cell is not vulnerable to bleomycin, in the postmitotic phase the drug may modify the synthetic mechanisms of cellular differentiation and thereby induce metaplasia.

Animals↗
PubMed1980

[BCG-induced production of a factor inhibiting macrophage migration and growth of melanoma B16].

The effect of BCG on the growth of melanoma B16 and production of the macrophage migration inhibitory factor (MMIF) by spleen lymphocytes as well as on phytohemagglutinin and tuberculin was studied in C57BL/6 mice. It was also studied how these parameters changed under the effect of transplanting splenocytes from syngeneic donors. Subcutaneous or intraperitoneal injection of BCG in a dose of 1 mg stimulated melanoma growth. Acceleration of the tumor growth entailed a more pronounced decrease in MMIF production. The inhibition of melanoma growth was noted after transplantation of splenocytes from syngeneic donors on the 11th day following inoculation of the tumor wherein MMIF production was normal. Transplantation of splenocytes from mice immunized with BCG resulted in an abrupt stimulation of melanoma growth and complete reversal of MMIF production by lymphocytes. The data obtained suggest the accumulation of suppressor cells by the spleen of mice treated with high doses of BCG, leading to the acceleration of melanoma B16 growth.

Animals↗
PubMed1979

Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin.

Toxins produced by Clostridium difficile have been implicated in the etiology of antibiotic-induced colitis. Clostridium difficile antitoxin is not available, but recent studies have shown that toxins present in the feces of patients with this disease are neutralized by Clostridium sordellii antitoxin. We found that C. sordellii antitoxin neutralized toxins produced in broth cultures of either C. sordellii or C. difficile and that passive immunization with C. sordellii antitoxin before challenge with clindamycin prevented colitis in hamsters. Significantly fewer antitoxin-treated animals than unimmunized controls developed diarrhea and died with hemorrhagic colitis. Administration of 300 U of antitoxin parenterally either on the day of challenge with clindamycin or 24 hr later provided significant protection (25% mortality vs. 100% mortality in controls, P less than 0.01). None of eight animals given antitoxin (300 U) both on the day of challenge and 24 hr later died. Filtrates prepared from cecal contents of dead or killed hamsters were tested for toxicity by intraperitoneal injection into hamsters and by addition to monolayers of monkey kidney cells. Fecal filtrates from antitoxin-protected animals were not toxic in these assays, but filtrates from control animals were uniformly toxic. Passive immunization against clostridial toxins was protective against clindamycin-associated colitis in this model. This finding further substantiates the importance of these toxins in the pathogenesis of antibiotic-induced colitis.

Animals↗
PubMed1995

Effect of N omega-nitro-L-arginine on working memory of rats in eight-arm maze task.

AIM: To study the effect of N omega-nitro-L-arginine (NNA) (a NO synthase inhibitor) on memory in the rats. METHODS: A delayed non-match-to-sample (DNMTS) eight-arm maze task was used to study spatial working memory. RESULTS: Intraperitoneal injection of NNA 100 mg kg-1 before the trial or at the start of the delay did not affect the accuracy, while pretraining administration of scopolamine 0.25 mg kg-1 produced impairment in mnemonic performance as evidenced by fewer correct choices after the delay and more total errors to complete the task. Intracerebroventricular infusion of NNA (10, 50, 100 nmol) did not affect the accuracy. CONCLUSION: A single ip or icv injection of NNA is not sufficient to alter the memory formation and use in this DNMTS eight-arm maze task.

Animals↗