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The influence of intraperitoneally injected 6-hydroxydopamine on electroshock seizure in chicks and rats.

1. 6-Hydroxydopamine, injected intraperitoneally in rats and chicks, did not induce spontaneous seizures but produced significant alterations in the threshold to electroshock seizure in chicks; the particular effects were dose-dependent and time-dependent. 2. Administration of 6-hydroxydopamine to 3 day old chicks and rats in the first and third days after birth resulted in an increase in the proportion exhibiting tonic seizure with electroshock when tested after 10-12 weeks. 3. When 6-hydroxydopamine was injected intraperitoneally into adult rats and cocks, there was no significant alteration in seizure threshold. 4. The results suggest that 6-hydroxydopamine penetrates the central nervous system of young chicks and rats and that adrenergic mechanisms are probably involved in modulating seizure mechanisms in both the chick and rat.

Animals

Bacteraemia in red mice (Clethrionomys g. glareolus Schreb.) after intraperitoneal injection of large doses of tubercle bacilli.

Römer (1903) has demonstrated that white mice injected intraperitoneally with large doses of tubercle bacilli isolated from man survived longer than mice injected with tubercle bacilli isolated from cattle. The blood of the spontaneously dead animals contained large numbers of tubercle bacilli. In the present study, red mice are injected intraperitoneally with 10 mg doses of different species of mycobacteria, and the number of bacilli in the blood is estimated at various intervals within the first 24 hours after the inoculation. The number of bacteria is considerably higher in the blood of mice injected with M. bovis, but, in contrast to M. bovis, M. avium disappears rapidly from the blood stream. Supplementary experiments show that red mice injected with M. bovis have a shorter survival time than mice injected with M. tuberculosis, and that the bacteraemia induced by M. bovis into white mice is clearly less pronounced than in red mice.

Animals

Intraperitoneally injected cholecystokinin-octapeptide activates pica in rats.

Cholecystokinin-octapeptide (CCK-8) was injected intraperitoneally into rats to see if it could cause them to eat kaolin (clay)--a pica behavior which has been shown to indicate gastric distress. In the first study, a single large dose of CCK-8 (20 micrograms/kg) failed to produce pica. In the second study, 4 smaller doses of CCK-8 (8 micrograms/kg), 30 min apart, produced significant ingestion of kaolin compared to the baseline condition of vehicle injections. The pica was comparable to that observed in another group of rats given a toxic dose of LiCl (127 mg/kg, IP). It is concluded that intraperitoneal injections of CCK-8 can induce a state of gastric distress in the rat.

Animals

Affinity of intraperitoneally injected activated carbon particles adsorbing mitomycin C to tumor surface of Yoshida sarcoma.

A new dosage form of mitomycin C (MMC-CH) comprising 0.75 mg/ml of activated carbon particles adsorbing mitomycin C at 124 micrograms/mg and 7 micrograms/ml of mitomycin C in a free state was injected intraperitoneally to male rats of Donryu strain transplanted intraperitoneally with 10(7) cells/rat of Yoshida sarcoma 4 days before injection. The rats were subjected to autopsy within 60 min after injection. MMC-CH adhered selectively to the tumor surface of Yoshida sarcoma growing intraperitoneally rather than to the surface of organs such as small intestines which the surface cancer did not affect. Within 120 min after injection, mitomycin C concentration in the tissue samples was bioassayed. Intraperitoneally injected MMC-CH distributed high levels of mitomycin C to the tumor rather than to the unaffected organ located intraperitoneally. Animals killed by cancer after the treatment of MMC-CH were autopsied. Histological effects of MMC-CH were studied microscopically. Mitomycin C adsorbed on activated carbon particles induced degenerative changes in the tissues of tumors to which the activated carbon particles had adhered.

Adsorption

Cellular reaction on the intraperitoneal injection of four types of polylactide particulates.

Four types of polylactide particulates, P-L-LA 100, 250, 550 KD and a P-DL-LA 400 KD were injected into the peritoneal cavity of mice. The inflammatory reaction showed an increase in cell number (mainly neutrophilic granulocytes) up to 48 h after which the cell numbers decreased below the control (phosphate-buffered saline). All four polylactide particulates aggregated and intermingled with inflammatory cells. The aggregates remained throughout the investigation period of 6 months. Quantitative measurements showed that standardization of the particle form and size is essential. From this study and other experiments in which calcium phosphates and asbestos were injected intraperitoneally, it is concluded that the inflammatory response observed in the peritoneal cavity is related to the type of material injected and probably to form and size of the individual particles, but not to molecular weight.

Animals

Biological activity of urease formulated in poloxamer 407 after intraperitoneal injection in the rat.

The advent of genetic engineering has resulted in a proliferation of protein pharmaceuticals available for a variety of therapeutic needs. However, the formulation and delivery of these proteins remain an intriguing challenge. Polymer-based protein drug delivery systems continue to be investigated, although many of the fabrication techniques used to incorporate proteins into the polymer matrix or device result in irreversible inactivation (denaturation) of the proteins. A well-characterized model enzyme, urease, was formulated in 33% (w/w) poloxamer 407 (Pluronic F-127) vehicle and injected intraperitoneally (ip) into rats in an attempt to achieve both preservation of biological activity and sustained release of the protein. The resulting ammonia concentration in plasma-time profiles were compared with those for rats injected with an identical dose (27.6 units of activity per 200 g of body weight) of urease dissolved in pH 7 phosphate buffer. Neither a pH 7 phosphate buffer solution nor poloxamer 407 (33%, w/w) dissolved in pH 7 phosphate buffer, when injected ip into rats, resulted in elevated ammonia levels in plasma. The time to reach a maximum ammonia level in plasma was increased approximately threefold following the injection of the urease-poloxamer 407 formulation, compared with that in control rats administered an identical dose of urease in solution. In addition, hyperammonemia was extended almost threefold in treated rats compared with control rats, without untoward effects. However, prolonged hyperammonemia in animals receiving an ip injection of the urease-poloxamer 407 formulation may have potentially resulted from the reduced clearance of ammonia and ammonium ion in the proximal tubules of the rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia

Experimental opacification of mediastinal lymph nodes by intraperitoneal injection of an iodinated fatty emulsion.

Absorption and lymphatic drainage of several lipiodol emulsions injected intraperitoneally have been studied in the rabbit and rat. Good opacification of the lymphatic channels and mediastinal lymph nodes is obtained in several hours with fine emulsions and in several days with coarse emulsions. The tolerance is related to dose, and the peritoneal reaction was moderate with the low doses, similar to that caused by the administration of physiologic saline alone. Computerized tomography in detecting low contrasts attained with small doses could render this method of indirect lymphography possible in man.

Animals

Mesothelial reaction of asbestos and other irritants after intraperitoneal injection.

Ten groups of rats were injected intraperitoneally with one of the following suspensions; (i) standard reference crocidolite; (ii) acid-treated crocidolite (iii) crocidolite plus iron oxide; (iv) crocidolite plus silica; (v) iron oxide; (vi) silica; (vii) long fibre crocidolite; (viii) short fibre crocidolite; (ix) long fibre glass and (x) short fibre glass. Two rats from each group were killed at 45, 90, 150, 240 and 330 days respectively, and the pathology induced by the different suspensions was studied histologically at each time interval. No evidence in support of the chemical induction theory or mechanical irritation theory in the pathogenesis of peritoneal mesotheliomas could be found, although all the suspensions except iron oxide caused a reactive mesothelium.

Animals

Effects of drugs on the acute inflammation following intraperitoneal injection of antigen into actively sensitised rats.

When actively sensitised rats were injected intraperitoneally with antigen, the local reaction that ensued can be divided into two phases: an immediate reaction characterised by histamine and SRS-A release with an associated extravasation of plasma proteins, and a later reaction involving infiltration of neutrophilic polymorphonuclear leucocytes. When the immediate reaction was modified by BRL 10833 (which inhibits histamine release from rat mast cells and reduces extravasation of plasma proteins), there was no reduction in neutrophil infiltration. FPL 55712, an SRS-A antagonist, also failed to inhibit neutrophil infiltration. The beta-adrenoreceptor stimulants isoprenaline and salbutamol reduced neutrophil infiltration. Isoprenaline inhibited the extravasation of plasma proteins when given before antigen, but even when administered to rats after antigen, when extravasation was complete, it still inhibited neutrophil infiltration. Propranolol reversed isoprenaline-induced inhibition of neutrophil infiltration.

Adrenergic beta-Agonists

[Comparative transmission and scanning electron microscopy studies of liver changes in mice followed sublethal skin burns and intraperitoneal injection of a specific skin burn toxin].

Ultrastructural alterations of the liver were examined on the 1st, 2nd, 3rd, 5th, 7th and 14th day after a standard burn in mice. Our results can be divided pathogenetically into two groups: 1. Alterations explained by the primary thermal injury including electron-optically empty vacuoles and sinusendothelium destruction. 2. Alteration due to the influence of a specific burn toxin including mitochondrial changes and the formation of autophagic vacuoles. Evidence of this distinction was produced by a second investigation. Burn toxin isolated from the serum of severely burned patients was injected intraperitoneally (15 mg) into 4 mice. The livers were examined by electron microscopy on the 2nd, 4th, 7th and 14th day. Alterations described in 2 above were not observed in any case of this investigation series. The nature and timing of liver alterations were similar to those described in 2 above. In none of the cases were changes similar to those in 1 above observed.

Animals

Repeated intraperitoneal injections of saline attenuate the antibody response to a subsequent intraperitoneal injection of antigen.

The results of two experiments with male C3H/HeJ mice indicated that repeated intraperitoneal (ip) injections of sterile saline over a 2-week period resulted in an attenuated antibody response to the subsequent ip injection of a soluble protein antigen, keyhole limpet hemocyanin. There were no differences among experimental groups that received a different number of preimmunization injections of saline, and comparable effects were obtained simply by the daily handling of mice. Neither repeated ip injections nor handling altered preimmunization (baseline) corticosterone levels, and only previously unmanipulated mice showed an elevation in corticosterone levels 30 min after ip immunization. These latter results suggest that the depressed IgM and IgG responses were not due to the immunosuppressive effects of endogenously elevated adrenocortical steroids.

Animals

Behavioral and neurochemical effects of intraperitoneally injected dendrotoxin.

Intraperitoneal administration of dendrotoxin, a polypeptide isolated from Dendroaspis angusticeps venom, provoked in mice the appearance of a complex stereotyped behavior including biting, head nodding, 'wet-dog' shakes and rearing. Signs of autonomic hyperactivity as well as hyperreactivity to sound and touch were prominent. Neurochemical analyses of monoamines and monoamine metabolites showed no change 90 min after dendrotoxin, with a decrease in dopamine concentrations and an increase in their metabolites in the striatum starting 3 hr later. Moreover, at this time, dendrotoxin also produced a significant increase of 5-hydroxytryptamine metabolites. These data are interpreted as indicating that dendrotoxin crosses the blood-brain barrier and provokes an increase of the activity at monoaminergic terminals.

Animals

The role of prostaglandins in the nociceptive response induced by intraperitoneal injection of zymosan in mice.

Intraperitoneal injection of zymosan (1 mg in 0.5 ml saline) in mice induces a transient writhing response accompanied by the synthesis of small amounts of prostaglandin E2(PGE2, less than 2 ng) and larger amounts of PGI2 (200 ng per mouse), measured as its non-enzymatic breakdown product, 6-keto-PGF1 alpha. Although both centrally-acting analgesics (morphine, clonidine) and prostaglandin biosynthesis inhibitors (aspirin, indomethacin, ibuprofen) blocked the writhing response to intraperitoneal injection of zymosan, only the latter reduced prostaglandin levels in the peritoneal cavity. The writhing response correlated equally well with PGE2 levels and 6-keto-PGF1 alpha levels when data from mice treated with centrally-acting analgesics were excluded. However, intraperitoneal injection of PGI2, but not PGE2, reversed the analgesia induced by indomethacin in zymosan-injected mice. Centrally-acting agents, but not ibuprofen, blocked the ability of PGI2 to reverse the analgesic activity of indomethacin. PGI2 (2 micrograms per mouse), injected intraperitoneally in otherwise untreated mice, induced writhing. These data indicate that PGI2 is the prostaglandin involved in mediation of the writhing response to zymosan and that prostaglandin biosynthesis inhibitors, but not centrally-acting analgesics, exert their analgesic activity by reducing the peritoneal level of PGI2. It is possible that PGI2 may have the ability to stimulate pain receptors directly in the mouse peritoneal cavity, in addition to its previously recognized ability to sensitize pain receptors to other pain-producing stimuli.

Animals

Labeling of the neurons of origin of zinc-containing pathways by intraperitoneal injections of sodium selenite.

Intraperitoneal injections of sodium selenite result in the formation of zinc-selenium complexes in zinc-containing axonal boutons ("Timm stainable boutons"), and the zinc-selenium precipitate can be rendered visible in histological sections by silver enhancement. In this work we present evidence, in the rat, that zinc-selenium precipitates formed in vivo after intraperitoneal injections of sodium selenite are translocated by colchicine-sensitive retrograde transport to neural perikarya when animals are allowed to survive 12-24 h after the selenite administration. Silver enhancement renders the perikaryal precipitates visible and thus demonstrates the perikarya of all zinc-containing neurons in the CNS simultaneously. Large populations of zinc-containing neurons identified by the method are found in layers II, III, and VI of all neocortical areas, in the superficial and deep layers of the prepyriform areas and, with a high degree of regional differentiation, in the retrosplenial, entorhinal, para- and presubicular cortices, the hippocampal formation and the amygdaloid complex. Zinc-containing cells were absent from the caudate-putamen, nucleus accumbens and septal complex. Labeled zinc-containing cells are absent in non-telencephalic parts of the brain. The findings indicate that the zinc-containing circuitry of the brain mainly serves in telencephalic information processing.

Animals

Poloxamer 407-mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection to rats.

Poloxamer (Pluronic) nonionic surfactant vehicles are a series of chemically-related block copolymers finding widespread use in parenteral formulations as solubilizing and wetting agents for traditional, low-molecular weight organic drug molecules, as well as stabilizing agents for proteins and polypeptide drugs. We report the effects of poloxamer 407 (Pluronic F-127) on plasma cholesterol and triglyceride concentrations in rats. Poloxamer 407 injected into rats by intraperitoneal injection (dose = 1.5 gm/kg) resulted in sustained (greater than 96 hour) hypercholesterolemia and hypertriglyceridemia. A larger dose of poloxamer 407 was required to elevate plasma triglyceride relative to total cholesterol. Ingestion of commercial rat chow had a negligible effect on plasma cholesterol and triglycerides levels in control (no poloxamer injection) animals, but consumption of food by animals that received an intraperitoneal injection of poloxamer 407 (30% w/w) resulted in significantly (p < .05) greater elevations in plasma cholesterol and triglycerides than in fasted animals administered poloxamer 407. The route of poloxamer 407 administration, namely intramuscular vs. intraperitoneal injection, was observed to be a more important factor for poloxamer-induced elevations in plasma cholesterol than poloxamer-mediated elevations in plasma triglycerides. Our results also provide suggestive evidence that the mechanism responsible for the elevation of plasma cholesterol following intraperitoneal injection of a poloxamer 407 solution (30% w/w) to rats may be due to stimulation of 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase activity in the liver by the poloxamer vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Biodistribution of indium-111-labeled OC 125 monoclonal antibody after intraperitoneal injection in nude mice intraperitoneally grafted with ovarian carcinoma.

The purpose of this work was to study the biodistribution of 111In-labeled OC 125 monoclonal antibody (MAb) with known affinity for ovarian carcinomas in a nude mouse model grafted i.p. with a human ovarian cancer (NIH:OVCAR-3). Tumor uptake 24 h after i.p. injection was higher with intact 111In-labeled OC 125 MAb (28 +/- 7.44%ID/g) than with 111In-nonspecific immunoglobulin (6.86 +/- 1.35%ID/g). The kinetics of tumor uptake also differed, showing a plateau followed by a drop at Day 7 with 111In-OC 125 MAb and a decrease beginning at 24 h with 111In-nonspecific immunoglobulin. Tumor-to-normal tissue ratios ranged between 29.91 +/- 11.85 and 0.68 +/- 0.15 with 111In-OC 125 MAb and between 4.50 +/- 1.06 and 0.53 +/- 0.04 with 111In-nonspecific immunoglobulin according to the normal tissues and the time points considered. Tumor uptake 2 h after injection was the same for F(ab')2 fragments as for intact MAb, whereas maximum uptake at 24 h (18.76 +/- 4.62%ID/g) was lower and was followed by a decrease at Day 4. Tumor-to-normal tissue ratios were in the same range, except for the tumor to blood ratio which was higher and the tumor to kidney ratio which was lower at 24 and 96 h. Maximum tumor uptake was higher after i.p. (30.77 +/- 4.76%ID/g) than i.v. (14.59 +/- 2.70%ID/g) injection. Instead of attaining the plateau noted after i.p. injection, tumor uptake after i.v. injection remained low at 2 h (2.11 +/- 1.66%ID/g), reaching its peak only after 96 h. 131I-OC 125 injected i.p., which reached maximum tumor uptake at 2 h (13.53 +/- 4.25%ID/g), showed tumor-to-tissue ratios ranging between 15.98 +/- 2.63 and 0.96 +/- 0.86, i.e., not very different from those with 111In. After i.p. injection of a radiolabeled colloid solution, maximum tumor uptake was reached at 96 h (20.22 +/- 5.35%ID/g), but with very high nonspecific uptake in liver (31.06 +/- 6.22%ID/g) and spleen (55.23 +/- 14.11%ID/g). These results indicate high, selective tumor uptake of 111In-OC 125 after i.p. injection and demonstrate the feasibility of i.p. radioimmunotherapy of ovarian carcinomas.

Animals

[Inhibition of the high-threshold calcium current in hippocampal neurons of rats subjected to intraperitoneal injection of phenylalanine].

Effect of intraperitoneal injection of phenylalanine on the calcium current of hippocampal neurons of rats has been studied by the voltage clamp method of the whole-cell recordings. Calcium currents in hippocampal neurons of control animals after 5-7 days in culture can be separated into two components: low and high voltage-activated ones. The value of high voltage-activated calcium current was 69 +/- 13% at Vt = -10 mV from total calcium inward current in these neurons. High voltage-activated Ica in neurons of phenylalaninemic rats was significantly depressed and its value was 32 +/- 14%, the Vt value being the same. Low voltage-activated calcium current was resistant to intraperitoneal injection of L-phenylalanine.

Animals

Cross-tolerance between inhaled cannabis and intraperitoneal injections of delta9-THC.

Male and female rats were exposed to Cannabis smoke or placebo once every second day for 32 days. Following these 16 trials all animals were injected once intraperitoneally with 4 mg/kg THC. After every third inhalation trial and after the injection the rats were placed on a movement sensor for 3 min. Cannabis smoke significantly reduced activity, relative to baseline scores, during the first 10 inhalation trials but by the thirteenth exposure, tolerance was evident. When the animals were injected with THC, the male rats who had been exposed to Cannabis smoke significantly increased their activity whereas the females did not alter their activity relative to the last inhalation trial. In contrast rats of both sexes that had been exposed to placebo smoke significantly decreased their activity following the injection. This intermodal cross-tolerance is discussed in terms of the role of conditioning in the development of tolerance.

Cannabis