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Increased local complement levels upon intraperitoneal injection of mice with Listeria monocytogenes and regulation by polyanions.

Alternative complement pathway activity in mouse peritoneal fluid was determined by a sensitive microtiter assay with rabbit erythrocytes as target cells and cobra venom factor as the inducer of bystander hemolysis. The intra- and interstrain variations in five mouse strains were 30% and, maximally, 64%, respectively. No activity was detected in genetically C5-deficient mice. In C5-sufficient mice, intraperitoneal injection of heat-inactivated Listeria monocytogenes resulted in a 250% increase in local complement activity within 30 min. This effect was reversed by simultaneous injection of dextran sulfate but not heparin. These results are discussed in relation to the ability of listeriae to activate the mouse alternative complement pathway in vitro and the effectiveness of dextran sulfate and the failure of heparin in functioning as an adjuvant in the induction of a protective response in mice by a heat-inactivated listeria vaccine.

Animals↗

Release site of TNF alpha after intravenous and intraperitoneal injection of LPS from Escherichia coli in rats.

Lipopolysaccharide (LPS) concentrations in the portal vein after intraperitoneal (i.p.) injection were slightly higher than those in the arteries. The tumor necrosis factor (TNF alpha) levels in arterial serum were higher after i.p. injection than after i.v. injection and rose to a peak at 90 min after some delay. Infusion of LPS into the portal vein increased the TNF alpha levels in the arterial serum. Pretreatment with indomethacin further increased the arterial levels of TNF alpha after portal infusion, but did not after them after i.p. injection, because of the reduction by indomethacin of LPS absorption after i.p. Injection of LPS. TNF alpha was also generated in the peritoneal cavity after i.p. injection of LPS. The TNF alpha concentrations in the arterial serum and in the peritoneal cavity were accelerated by mast cell degradation. In conclusion, TNF alpha was generated mainly in the liver, but also in the peritoneal cavity, after i.p. injection of LPS, and was negatively regulated by prostaglandins.

Animals↗

Pathology of tumors developed in guinea pigs given intraperitoneal injections of N-methyl-N-nitrosourea.

The carcinogenic effects of N-methyl-N-nitrosourea after repeated intraperitoneal administration in inbred strain NIH 13 guinea pigs were studied. 50% of the animals that survived beyond 22 weeks, after intraperitoneal injection of MNU at a dose of 10 mg/kg body weight/week for 18 weeks, developed a broad spectrum of tumors: these included adenocarcinoma of pancreas in 2 animals, fibrosarcoma of the mesentery in 2 animals, angiosarcoma of mesentery in 2 animals, mesothelioma of the peritoneum in 1 animal and tumors of small intestine in 3 animals. These studies indicate the susceptibility of different types of tissue to the local effects of MNU after intraperitoneal administration.

Adenocarcinoma↗

Acute nephrotoxicity as an adverse effect after intraperitoneal injection of massive amounts of bioactive ceramic powders in mice and rats.

Silicon elution from bioactive ceramic powders was measured using an in vitro solubility test, in which the powders were soaked in phosphate buffer solution. Silicon elution was highest in Bioglass (BG), followed by Ceravital (KGS), apatite-wollastonite-containing glass ceramics (A-W.GC), and hydroxyapatite (HA), respectively. Silicon elutions on this in vitro solubility test were correlated with the rates of rapid death in mice following intraperitoneal injection of each of these bioactive ceramic powders. Histopathological examination of the mice revealed nephropathy, which was considered to be the cause of death. The nephropathy was characterized by epithelial degeneration in the renal tubules and increased silicon content throughout the entire kidney, findings suggesting silicon nephropathy. It is considered that, because a large quantity of silicon eluted from the powder was absorbed from the peritoneum, concentration in the glomerular filtrate and urine increased until silicon polymerization occurred, after which the silicon polymer became deposited in the renal tubules. A single injection of furosemide prevented the acute nephrotoxicity of bioactive ceramic powder.

Animals↗

Distribution of 3-hydroxy fatty acids in tissues after intraperitoneal injection of endotoxin.

BACKGROUND: 3-Hydroxy fatty acids (3-OH FAs) with 10- to 18-carbon chain lengths are constituents of the endotoxin [lipopolysaccharide (LPS)] of gram-negative bacteria. We investigated whether these FAs may be used as chemical markers in measuring endotoxin concentrations in mammalian tissue samples. METHODS: We used gas-liquid chromatography-tandem mass spectrometry to measure 3-OH FAs in serum and tissues (heart, liver, and skeletal muscles) of rats after intraperitoneal injection of Escherichia coli LPS. One group of rats (group I) received a single LPS dose of 20 mg/kg of body weight; group II rats received the same total dose but over the course of 10 days (2 mg/kg each day). Rats receiving saline (group III) were used as controls. RESULTS: 3-OH FAs with chain lengths of 10, 12, 14, 16, and 18 carbons were detected in all studied types of samples. Group I rats had 50-fold and group II rats had 3-fold higher serum concentrations of 3-hydoxytetradecanoic acid (3-OH 14:0, the predominant 3-OH FA of E. coli LPS) than group III rats. Concentrations of 3-OH 14:0 in livers from group I and II rats were similar and fourfold higher than in group III rats, whereas concentrations of the same acid in skeletal and heart tissues did not differ among the three groups of rats. 3-OH 14:0 dominated in heart and liver of group III rats, whereas 3-OH 16:0 (followed by 3-OH 14:0) dominated in skeletal muscles and blood. CONCLUSIONS: 3-OH FAs 10-18 carbons in length, probably originating from endotoxin and mitochondrial beta-oxidation, are abundant in rat liver, skeletal muscles, and heart and can also be detected in blood. The widespread presence of these compounds in mammals limits their usefulness as LPS markers for endotoxin in clinical samples.

Animals↗

[Immune complex induced rat liver fibrosis model by intraperitoneal injection of human serum albumin].

BACKGROUND: To establish an immune complex induced rat liver fibrosis model by intraperitoneal injection of human serum albumin (HSA). METHODS: Male Wistar rats, weighting 110-120 g, were sensitized with HSA by subcutaneous injections at different sites for 4 shots at intervals of 14, 10 and 10 days. Ten days after the fourth injection, the peritoneal booster dose of HSA was administrated to rats twice weekly for 8 weeks with an initial dose of 5 mg, and progressive increase to 20 mg. Liver biopsy was performed at the beginning of HSA booster, 15, 30, 60 days after HSA booster, and 30, 60, 90, 120 days after discontinuation of HSA booster, respectively. Liver samples were examined for histological changes and liver hydroxyproline (HyP) was measured by biochemical method. Fibrosis serum markers hyaluronate acid (HA) and laminin (LN) were determined by RIA method. RESULTS: After intraperitoneal administration of HSA, the degree of liver pathological changes, the liver Hyp content and serum HA and LN increased (P<0.05). The longer the HSA administrated, the higher the liver pathological change degree (P<0.05) and the levels of liver Hyp and serum HA (P<0.01). After discontinuation of HSA, the levels of serum HA and liver Hyp decreased significantly (P<0.01) but were still significantly higher than those in the controls (P<0.01). The liver fibrosis formation rate was 100% and the fibrosis lasted more than 120 days. CONCLUSION: Intraperitoneal administration of HSA to make rat immune complex induced liver fibrosis model is convenient with high liver fibrosis formation rate and long fibrosis lasting time. The model may be used to evaluate the therapeutic effect of antifibrotic drugs.

Animals↗

Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice.

A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon. n-Hexadecane (C(16)H(34)), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 ml of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer>1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases.

Alkanes↗

The recovery of slow axonal transport after a single intraperitoneal injection of beta, beta'-iminodipropionitrile in the rat.

A single intraperitoneal injection of beta, beta'-iminodipropionitrile (IDPN) at a dose of 1.5 g/kg was given to 4-week-old rats. Immediately following, or at 1, 2, 3, 5, 10, and 15 weeks after IDPN injection, [35S]methionine was introduced into the anterior horn area of the lumbar cord. Labeled axonal proteins in the sciatic nerve were analyzed electrophoretically and fluorographically at 5, 10, and 15 weeks post-labeling. Labeled neurofilament proteins halt for a short period just after IDPN injection, then continue migrating distally, though at a slower rate, and finally the transport of affected neurofilament proteins completely recovers by 6 weeks post-labeling.

Animals↗

Rapid induction of uterine endometrial proliferative lesions in transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) given a single intraperitoneal injection of N-ethyl-N-nitrosourea.

In our previous study, uterine endometrial stromal sarcomas and atypical hyperplasias of the endometrial glands were induced in heterozygous p53 deficient mice (p53 (+/-) mice) of the CBA strain given a single dose of N-ethyl-N-nitrosourea (ENU). In order to clarify whether uterine tumors can be induced in transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) that are very susceptible to genotoxic carcinogens, rasH2 mice and their wild-type littermates received an intraperitoneal injection of 120 or 0mg/kg body weight of ENU followed by no further treatment for 22 weeks. Eighteen and 94% of ENU-treated rasH2 mice had uterine endometrial adenocarcinomas and atypical hyperplasias, respectively. Other malignant and benign tumors such as lung alveolar/bronchiolar adenomas and carcinomas, forestomach squamous cell papillomas and carcinomas, splenic hemangiomas/sarcomas, skin papillomas, malignant lymphomas and harderian gland adenomas were also observed in ENU-treated rasH2 mice. The result in the present study suggests that female rasH2 mice are very susceptible to uterine carcinogenesis, providing a useful model for ENU-induced uterine epithelial tumors.

Adenocarcinoma↗

CT demonstration of peritoneal metastases after intraperitoneal injection of contrast media.

Thirty-three patients with ovarian carcinoma who had no evidence of metastases or ascites demonstrated on computed tomography (CT) with and without contrast agent were examined with CT after injection of approximately 3000 cc of a 2.4% solution of nonionic contrast media into the peritoneum. After intraperitoneal injection with CT (IPC CT), 22 were diagnosed as having intraperitoneal metastases. Of these, 19 were found to be true positives and 3 false negatives. Three other patients diagnosed as normal were found to have metastases. In all patients the peritoneum was well outlined and generally any metastases smaller than 1 cm were demonstrated. It was possible to identify compartmentalization of the peritoneum and to determine the location of the lesion to be in the peritoneum or the extraperitoneal space. This information is necessary in the planning of chemotherapy, particularly endoperitoneal chemotherapy. Tiny metastases to the omentum or adherent loops of small bowel could not be seen well.

Female↗

Tissue tumor necrosis factor mRNA expression following cecal ligation and puncture or intraperitoneal injection of endotoxin.

Tumor necrosis factor (TNF) has been implicated as a key mediator of the septic response. Although very high serum levels of TNF are detected in animal models of endotoxemia or gram-negative bacteremia, human patients with sepsis rarely have greatly elevated TNF serum levels. It has therefore been postulated that TNF may act in a paracrine fashion to cause local injury. In order to examine the role of locally produced TNF in sepsis, we compared serum TNF levels and TNF messenger RNA (mRNA) expression in various tissues following cecal ligation and puncture (CLP) or intraperitoneal injection of a sublethal dose of endotoxin. TNF mRNA expression was determined by the reverse transcription differential polymerase chain reaction using beta-actin as an internal standard. Serum levels of TNF were threefold higher after endotoxin administration compared to CLP. TNF mRNA in peritoneal macrophages rose fourfold after both endotoxin injection and CLP, with rapid return to normal in endotoxin-treated animals. There was a significant increase in TNF mRNA in the liver and lung, but not the spleen, during the first 24 hr after CLP. An increase in TNF mRNA was seen in all three tissues after injection of endotoxin. These results support the concept of locally produced TNF as a contributing factor in tissue damage and multiple organ failure during sepsis.

Animals↗

A CT using longitudinally detected ESR (LODESR-CT) of intraperitoneally injected nitroxide radical in a rat's head.

We have developed an in vivo longitudinally detected ESR (LODESR) imaging system operating at 700 MHz based on a loop-gap resonator and a pair of saddle-type pickup coils. A good linear relationship between the LODESR signal intensity and the applied power in a range up to 15.8 W was obtained. The detection of LODESR signals was barely affected by variations in the resonant properties. The characteristic of LODESR is suitable for in vivo examination. Using this system, we succeeded in obtaining LODESR-CT images of the head region of a rat after the intraperitoneal injection of a nitroxide radical.

Animals↗

The effect of dietary or intraperitoneally injected seaweed preparations on the growth of sarcoma-180 cells subcutaneously implanted into mice.

Sixteen preparations from 9 edible seaweeds including powdered weed (P), hot-water extract (E), the non-dialyzable fraction (I) of E and the residue (R) of hot-water extraction were incorporated into a basic diet, and they were given to mice implanted with Sarcoma-180 cells s.c., for 5 weeks. Consequently, diets with 6 preparations, E of Laminaria angustata, P and E of Laminaria angustata var. longissima, and P, E and R of Laminaria japonica var. ochotensis, were found to be effective, with inhibition ratios ranging from 70.3% to 83.6%. Intraperitoneal injection of 10 preparations from 6 edible seaweeds, including the above 3 weeds, were also noted to be effective in the same test system, with inhibition ratios ranging from 61.9% to 95.2%.

Animals↗

[Changes in bioelectric function of rabbit cerebral cortex after intraperitoneal injection of organic solvents. I. Toluene and m-xylene].

The goal of the study was to implement the method and to use it in identifying the extent of neurotoxic effect of organic solvents on the basis of changes in spontaneous (EEG) and evoked (evoked potentials) function of cerebral cortex and hippocamp induced under conditions of single exposure. Electrophysiological experiments were performed on rabbits with electrodes chronically implanted into selected structures of the brain. The examinations revealed quantitative differences in the postinjection EEG picture of cerebral cortex and hippocamp as well as in morphology of potentials evoked by visual stimulus and electric irritation of the brain. Concentrations of solvents in peripheral blood were determined on rabbits nonoperated by gas chromatography linked with a head-space technique. Ten and thirty minutes after intraperitoneal injection of equimolar quantities of organic solvents higher concentration of toluene when compared to the of m-xylene was found in the blood of experimental animals.

Animals↗

Intraperitoneal injection of genetically modified, human mesothelial cells for systemic gene therapy.

An ideal cell type for ex vivo gene therapy should be easy to biopsy, propagate, and genetically engineer in culture, should be transplantable using simple procedures, and should express therapeutic proteins at useful levels. The mesothelial cell appears to satisfy these criteria. Several thousand proliferative mesothelial cells were present in typical specimens of nonpathologic human peritoneal fluid obtained by needle aspiration. These divided rapidly in a specialized medium to yield pure cultures of approximately 10(7) cells within 2 weeks. The replicative lifespan of mesothelial cells cultured from adults was approximately 42-52 population doublings, permitting expansion and cryopreservation of a lifetime supply of autologous cells from one fluid sample. Cells transduced with a human growth hormone (hGH) adenoviral vector secreted 100-300 microg of hGH/10(6) cells per day for at least 6 weeks in culture when maintained at quiescence. Intraperitoneal injection of transduced cells into athymic mice resulted in rapid systemic delivery of hGH, with peak plasma levels of 0.1-1 microg/ml declining over 3 weeks to <1 ng/ml. Mice receiving a second injection of engineered cells displayed the same plasma hGH levels and duration as naive mice. Cells labeled with a beta-galactosidase vector were identifiable by in situ enzymatic staining as clusters attached to peritoneal surfaces at multiple sites for at least 19 days after injection. Cells serially passaged through about three-quarters of their lifespan before transduction and injection were as effective at hGH delivery as earlier-passage cells. These results indicate the clinical potential for ex vivo gene therapy using mesothelial cells.

Adenoviridae↗

Effect of intraperitoneal injection volume and antibody protein dose on the pharmacokinetics of intraperitoneally administered IgG2a kappa murine monoclonal antibody in the rat.

The i.p. route of antibody administration offers a regional delivery advantage to the peritoneal cavity. In an effort to optimize this method of delivery, the volume of i.p. injection and total protein dose were examined for their effect on the absorption and disposition of an IgG2a kappa murine monoclonal antibody. 5G6.4, administered i.p. Normal rats (Sprague-Dawley) were given one of two protein doses (1-2 or 100 micrograms) of 125I-5G6.4 in a 2.0-ml i.p. injection volume. In both cases the same radiation dose (approximately 20 mu Ci/rat) was administered since only the tracer level (1-2 micrograms) was labeled. Hence, the 100-micrograms dose consisted of approximately 2 micrograms of labeled antibody with 98 micrograms of unlabeled antibody. In a separate experiment, two i.p. injection volumes (2.0 or 20.0 ml) of 125I-5G6.4 (approximately 20 mu Ci/rat) were administered to normal Sprague-Dawley rats. Pharmacokinetic modeling of the whole blood radioactivity levels was undertaken for both groups. The liver, kidney, muscle, lung, diaphragm, and anterior mediastinal lymph nodes were excised upon sacrifice and tissue levels at sacrifice were recorded. The volume of i.p. injection is shown to be a significant factor with respect to i.p. transport. Maximum concentration in the blood, Cmax, was reduced (P less than 0.1) and time of maximum concentration, tCmax was prolonged (P less than 0.05) from 8.4 h (in the 2-ml group) to 14.5 h (in the 20-ml group). Both contribute to a modest reduction in AUC(0----infinity) (P less than 0.15) in which AUC is the area under the concentration-time curve. The increase in blood clearance, Clb, at the higher injection volume (0.287 ml/h for the 20-ml volume and 0.194 ml/h for the 2-ml volume) is presumably due to increased diuresis resulting from autoregulation of fluid removal via lymphatic drainage. Volume of distribution, Vd, is increased since Vd and Clb are functionally proportionate and elimination is assumed constant. Tissue levels at sacrifice, except for the thyroid and anterior mediastinal lymph nodes, were the same. Mean thyroid levels were reduced in the 20-ml group (P less than 0.05) by 22.5%, likely as a result of increased diuresis. Increased nodal uptake (P less than 0.01) can be attributed to the dilution effect of the bolus injection. The rate of mass transfer is greater for the 2-ml group up to 4 h postinjection. Subsequently, the mass transfer rate is greater for the 20-ml group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Selective induction of prostate carcinomas in F344 rats treated with intraperitoneal injections of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl.

Groups of F344 and Wistar rats were given an intraperitoneal injection of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMAB) at a dose of 5 mg/kg body weight with a 1-week dietary pretreatment with ethinyl estradiol (EE), and this regimen was repeated 10 times at one-week intervals. Additional groups were given N-OH-DMAB 10 times without the dietary EE pretreatment. The total experimental period was 60 weeks. Carcinomas and atypical hyperplasias of the prostate developed in 8 (42%) and 16 (84%) of 19 F344 rats without the dietary EE treatment and in 1 (6%) and 7 (39%) of 18 rats with the EE diet, respectively. No prostatic tumors were found in Wistar rats, although atypical hyperplasias were observed in 6 of 18 rats with and 4 of 8 rats without the EE supplementation. Tumor yields in other organs were extremely low, resulting in good survival of the animals. A comparison of the results with those obtained for DMAB suggests that intraperitoneal administration of N-OH-DMAB in F344 provides a better induction method for models of prostate carcinogenesis.

Aminobiphenyl Compounds↗

Natural history of TCDD-induced liver lesions in rats as observed by transmission electron microscopy during a 32-week period after a single intraperitoneal injection.

Forty-two male rats were injected with a single intraperitoneal dose of TCDD in acetone and corn oil and sacrificed after 2, 4, 8, 16, 24, and 32 weeks, to study the long-term effects of a single injection. The liver lesions become progressively worse up to the 16th week and appear thereafter to slowly regress.

Animals↗