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At least 217 records · Page 12Linked to original sources

Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1-methyl-1-nitrosourea.

Dose-response relationships for the induction of mammary tumors by a single i.p. injection of 1-methyl-1-nitrosourea (MNU) were studied. Groups of 30 female Sprague-Dawley rats were given i.p. injections of 50, 37.5, 25, 12.5, or 0 mg MNU/kg body weight at 50 days of age. Animals were palpated for tumor detection twice weekly throughout a 28-week observation period. Administration of MNU i.p. caused no acute toxicity. Both benign and malignant mammary tumors were induced by MNU, but malignant tumors appeared earlier and at a faster rate than benign tumors. The incidence and numbers of mammary carcinomas increased whereas median cancer-free time decreased with increasing dose of MNU. Approximately twice as many mammary cancers were observed in the cervical-thoracic as in the abdominal-inguinal mammary gland chains irrespective of carcinogen dose, while the frequency of tumor occurrence in the left versus right chains was similar. Tumor latency decreased with increasing dose of MNU, but the quartiles for time to detection of all tumors within each carcinogen dose group were similar irrespective of anatomical region in which the tumors occurred. The mammary tumor response attained via i.p. injection was similar but the coefficient of variation for tumor multiplicity within a carcinogen dose group was lower in comparison to that observed when MNU was administered i.v. or s.c. Among these techniques for carcinogen injection, the i.p. route is the most rapid method and offers an added advantage of ease of administration with quantitative, reproducible delivery of the desired amount of carcinogen and a decrease in variability of tumor response among animals within a treatment group. This method is well suited for the technically less experienced investigator and for those in need for a rapid method of injecting MNU to large numbers of animals.

Animals↗

[Effects of intraperitoneal injection of naloxone on the analgesic effect and the changes of brain catecholamine contents induced by electroacupuncture in rats].

Rats were randomly divided into 4 groups: Control, Electro-acupuncture (EA), Naloxone and Naloxone plus EA. The content of noradrenaline (NA) and dopamine (DA) in brain stem, diencephalon and telencephalon were determined by spectrofluorometry. It was found that the pain threshold increased and the NA content in the telencephalon decreased and the DA level in the brain stem increased markedly after EA. Naloxone injection partially decreased the analgesic effect of EA and abolished the EA-induced elevation of DA in the brain stem and attenuated the NA level in the diencephalon after EA. These results suggest that morphine receptor may play an important role in EA analgesia and this may be partially carried out through the brain catecholamine system.

Animals↗

Biodistribution of indium-111-labeled OC 125 monoclonal antibody intraperitoneally injected into patients operated on for ovarian carcinomas.

The biodistribution of 111In-labeled monoclonal antibody (MAb) OC 125 was studied after i.p. injection in 28 patients who underwent surgery for ovarian carcinoma. Group I (eight patients) received intact 111In-labeled OC 125 MAb, Group II (three patients) intact 111In-labeled irrelevant NS, Group III (five patients) intact 111In-labeled OC 125 MAb associated with 20 mg of the same unlabeled MAb and Group IV (12 patients) F(ab')2 fragments of 111In-labeled OC 125 MAb. The patients were operated on 1 to 3 days after i.p. injection, and the surgeon removed large tumor fragments and/or small tumor nodules and, in some patients, collected the residual perfusion fluid from which malignant cell clusters were isolated. Uptake by large tumor fragments at 24 h was low: 0.0031 +/- 0.0032% injected dose per gram (%ID/g) for Group I and 0.0024 +/- 0.0022%ID/g for Group IV. It was moderately higher than that of Group II (0.0014 +/- 0.0006%ID/g) and Group III (0.0015 +/- 0.0007%ID/g). Uptake by small tumor nodules (0.1302 +/- 0.0802%ID/g at 72 h for Group I) and malignant cell clusters (median: 0.3322, with a maximum value of 4.1614%ID/g at 24 h for Group IV) was markedly higher. Tumor-to-normal tissue ratios with OC 125 MAb [intact or F(ab')2 fragments] ranged between 0.1 and 8.5 for large tumor fragments and 2 and 8,700 for small tumor nodules and malignant cell clusters. It would thus appear that RIT is feasible if an appropriate radionuclide can be selected for antibody labeling.

Adult↗

Hepatocarcinogenicity of benzo[a]pyrene to rainbow trout by dietary exposure and intraperitoneal injection.

The influence of benzo[a]pyrene [(BP) CAS: 50-32-8] on the induction of certain enzymes within the hepatic mixed-function oxidase (MFO) system and its potential carcinogenicity were examined in rainbow trout (Salmo gairdneri). Nine-week feeding trials were performed with 500 and 1,000 ppm BP to determine trout tolerance to BP. Levels of MFO enzymes, including ethoxyresorufin-O-deethylase (EROD), ethoxycoumarin-O-deethylase (ECOD), benzo[a]pyrene monooxygenase (BPMO), and cytochrome P450 were measured during this time. An 18-month feeding trial of a 1,000-ppm BP dose was initiated in duplicate groups of 100 fingerling rainbow trout. Samples of trout were killed at 6, 12, and 18 months for gross and histologic examination of the internal organs for neoplasms. A group of fifty 10-month-old rainbow trout were given 12 monthly ip injections of 1 mg BP in 0.4 ml propylene glycol (PG), and comparable controls were given PG injections only. The trout were held for an additional 6 months, killed at age 28 months, and examined as in the dietary study. Mean MFO enzyme levels of EROD, ECOD, BPMO, and cytochrome P450 were significantly (P less than .001) elevated, showing dose- and time-response relationships when compared to MFO enzyme levels in control fish. Twelve months after BP exposure was initiated, 15% of the BP-fed fish had histologically confirmed neoplasms of the liver. After 18 months the incidence increased to 25%. No evidence of neoplasia was observed in control fish. BP injected ip resulted in a 50% incidence of hepatocellular neoplasms and in a fibrosarcoma of the liver and papillary adenomas of the swim bladder in 1 fish. These results indicate that BP is a potent inducer of selected hepatic MFO enzymes and establish, for the first time, the hepatocarcinogenicity of BP in an aquatic species.

Adenocarcinoma↗

Metabolism of 24-ethyl-4-cholesten-3-one and 24-ethyl-5-cholesten-3 beta-ol (sitosterol) after intraperitoneal injection in the rat.

14C-labeled C29- and C27-steroids were injected in rats, which were killed after 14 days. Phytosterols (C29) were excreted mainly as such, whereas C27-steroids were recovered essentially as water soluble metabolites. The total 14C-excretion was lower from 3-oxo, delta 4-steroids (5 alpha-stanol precursors) than from 3 beta-hydroxy,delta 5-steroids. 14C-Phytosterols were accumulated more than C27-steroids in liver, serum (mainly in HDL) and especially in adrenal glands and ovaries. In relation to serum, particularly the 5 alpha-stanols were enriched in the adrenal glands and ovaries. No striking lysosomal accumulation of any of the steroids was found.

Animals↗

Cytotoxic lymphocytes in rat tumor in situ: effect of intraperitoneal injections of Propionibacterium avidum.

In vitro cytotoxicity against tumor cells of lymphocytes in sc implanted BC47 bladder tumor of ACI/N rats with or without Propionibacterium avidum (P. avidum) treatment was studied. Tumor-associated lymphoid cells (TAL) were obtained from tumor tissues by mechanical treatment (NDi fraction) and by enzymatic treatment with Dispase I, a proteolytic enzyme (Di fraction), followed by passage through glass wool columns to deplete tumor cells. NDi fraction of TAL from P. avidum-treated animals showed a significant cytolytic activity against BC47 cells, but not against other ACI/N bladder tumor cell lines, BC12 and BC50. These TAL lost the cytolytic activity on treatment with anti-rat thymocyte serum or anti-rat T cell monoclonal antibodies, R1-3B3 and R1-10B5, and complement. Natural killer activity determined with YAC-1 cells was low in the cells of NDi fraction and scarcely detectable in the cells of Di fraction from both P. avidum-treated and untreated rats. These results indicate that the antigen-specific cytotoxic T cells in the tumor in situ are induced by in vivo P. avidum treatment. On the other hand, P. avidum treatment augmented nonspecific cytolytic activity of peripheral lymphoid cells such as plastic-nonadherent peritoneal cells, spleen cells and blood lymphocytes in normal and BC47-bearing rats. However, the antigen-specific cytolytic T cells were predominantly induced and recovered in the plastic nonadherent peritoneal cells of BC47-bearing rats by the treatment with P. avidum.

Adjuvants, Immunologic↗