Corticosterone and muscle protein breakdown in vivo in rats: effect of subcutaneous and intraperitoneal injection.
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In experiments on mice 3H-spiperone binding after intraperitoneal injection was studied. The binding of 3H-spiperone was saturable in the frontal cortex and subcortical structures, whereas in the cerebellum, the amount of radioactivity increased in a linear manner and was referred to as nonspecific binding. The neuroleptics haloperidol, chlorpromazine and sulpiride given 0.5 h before 3H-spiperone displaced 3H-spiperone in the subcortical structures in a dose-related manner. Although the level of the specific 3H-spiperone binding after intraperitoneal injection was lower than after intravenous injection, the intraperitoneal method is simpler, well reproduced and given results comparable with the intravenous method.
Intraperitoneal administration of docetaxel has been used to treat peritoneal dissemination of cancer, but its safety has not yet been confirmed. We have compared the pharmacokinetic behaviour of docetaxel after intravenous and intraperitoneal administration in CD-1-nu/nu mice bearing MKN45P, a gastric cancer variant line producing peritoneal dissemination. Docetaxel (8 mg kg(-1)) was intravenously or intraperitoneally injected into the mice and at designated times the drug concentration was measured in plasma, ascites fluid, and abdominal tissues (liver, kidney, intestine and spleen, solid cancer, and suspended free cancer). The pharmacokinetic behaviour of docetaxel was similar in control mice and cancer-bearing mice after administration via either route, except that the transfer of docetaxel from the abdominal cavity to systemic blood (plasma) was slower in cancerbearing mice than in control mice. As expected, the intraperitoneal drug concentration was much higher (approximately 100-fold) and was maintained for a longer time in the intraperitoneal injection group than in the intravenous injection group. The drug concentrations in peritoneal solid cancer tissue and suspended free cancer cells were also significantly higher for a longer time in the intraperitoneal injection group than in the intravenous injection group. The values of the plasma area under concentration-time curves (AUC) were similar for both administration routes. The ratio of AUC ascite/AUC plasma after intraperitoneal administration was higher than after intravenous administration. The drug concentration in abdominal organs after intraperitoneal injection was lower during the first 2 h, then became similar to those after intravenous injection. These results indicated that the intraperitoneal administration of docetaxel for peritoneal dissemination was likely to be an effective treatment method, without causing any increase in systemic toxicity.
Intraperitoneal injection in adult male rats with adrenocorticotrophic hormone (ACTH) (0.6 mU daily for 3 days) brought about a marked decrease in the activities of four thymic enzymes studied: glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, isocitric dehydrogenase, malic dehydrogenase. A prominent rise in the levels of these enzymes occurred when ACTH was replaced by corticosterone (1 mg injected daily for 3 days). In adrenalectomized rats, the results were similar to those observed in intact animals. The significance of an increase in transaminase activities after corticosterone treatment, relating to an increase in citric cycle enzymes is discussed. On the other hand, it was suggested that ACTH exerts an extra adrenal effect on the thymus.
Unimmunized chickens, given intraperitoneal injections of Sephadex at the same time that they were inoculated with oocysts of either Eimeria tenella or E. acervulina, had significantly lower lesion scores at 6 days postinoculation (PI) than unimmunized chickens that were injected with saline instead of Sephadex. Despite the difference in lesion scores, there was little effect on weight gain, except in one experiment, in which Sephadex-injected chickens gained significantly more weight than saline-injected chickens. In contrast, in chickens that were immunized by prolonged exposure to sporozoites of E. adenoeides, injection of Sephadex at the time of challenge with E. tenella did not reduce lesion scores or parasite development as compared with the uninjected chickens, and the weight gain of the Sephadex-injected challenged chickens fell to a level significantly lower than that of their saline-injected challenged counterparts. The data indicate that Sephadex injected at the time of oocyst inoculation 1) produces markedly different effects on lesion scores and weight gain in unimmunized and immunized chickens and 2) abrogates sporozoite-elicited immunity against E. tenella challenge.
The effect of intraperitoneal injection of Vinblastine sulfate on rat periodontal ligament was studied. Cells still synthetize collagen after 2 hours of the injection with evidence of loss of extracellular collagen fibers orientation. Tubular lysosome could not be detected after 2 hours with formation of lysosomal clusters in the cell center. After 4 hours of administration, evidences of cell degeneration were observed. The present study has shown that Vinblastine produces effect on fibroblasts as early as two hours after injection.
Intraperitoneal injection of 0.15 M LiCl (2% body weight) to anaesthetized rats elicited, after a 6 min latency, discharge of about 50% units i basolateral amygdala (n = 27). The activation lasted for 15 min on the average. Cortical neurones were not affected by the LiCl injection. It is suggested that the amygdalar reaction to LiCl administration may account for the association of the gustatory trace with the visceral signals of poisoning which mediates acquisition of conditioned taste aversion under anaesthesia.
Intraperitoneal injection of glycopeptidolipid (GPL) antigens from Mycobacterium avium complex serovar 4 resulted in the decreased ability of murine splenic lymphocytes to respond to nonspecific-mitogen-induced blastogenesis when exposed to concanavalin A, phytohemagglutinin, and lipopolysaccharide. Adherent cell depletion and cell mixing experiments with T lymphocytes indicated that macrophages were not a major contributor to the immunosuppression observed in this study. Enumeration of splenic lymphocytes by means of flow-cytometry with fluorescein isothiocyanate-conjugated monoclonal antibodies demonstrated that intraperitoneal injection of GPL antigens resulted in a significant decrease in Thy-1+ and Lyt-1+ cells but no change in the numbers of Lyt-2+ cells. Treatment with GPL antigens in vitro affected the ability of splenic mononuclear cells to respond optimally for concanavalin A-induced blastogenesis at 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml and lipopolysaccharide-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. However, in vitro treatment with GPL antigens did not affect phytohemagglutinin-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. These findings suggest that GPL antigens or their metabolites affect lymphocyte function and may be important cofactors in the overall pathogenesis of M. avium complex infections.
We hypothesized that intraperitoneal injections of anaesthetics or fluid per se might evoke a delayed preconditioning-like response in mice hearts isolated and Langendorff perfused 24 h later. To test this, mice were given opioid anaesthesia by intraperitoneal injections or sham treated and the hearts were harvested and subjected to global ischaemia and reperfusion 24 h later in series 1. In series 2, mice were subjected to intraperitoneal injection of Ringer, sham needle prick procedure, or no intervention 24 h before heart isolation. In series 3, intraperitoneal Ringer injection 24 h earlier was compared with the effects of classic preconditioning or no pretreatment of the isolated heart or no treatment. Heart function was measured in all series. At the end of reperfusion, hearts in series 1 and 2 were frozen and infarct size was estimated by triphenyltetrazolium chloride solution. In series 3, separate hearts were frozen for immunoblotting to detect phosphorylation of mitogen-activated protein (MAP) kinases. Cardiac activation of nuclear factor kappa B (NFkappaB) was measured using a NFkappaB luciferase firefly reporter mouse. The ischaemia-induced impairment of left ventricular function was attenuated by opioid anaesthesia injected 24 h earlier, which also reduced infarct size. Injection of fluid, but not the sham needle prick procedure, reduced infarct size. The functional protection afforded by classic preconditioning and Ringer pretreatment was comparable. Neither cardiac MAP kinases nor NFkappaB were influenced by the interventions. In conclusion, this study demonstrates a delayed preconditioning-like effect of the heart caused by intraperitoneal administration of opioid anaesthetics and of fluid only in the mouse. The mechanism of protection remains to be determined.
The carcinogenic effect of a single intraperitoneal injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN) was studied in male Wistar rats for 52 weeks. Adenomas were induced in 100% of rats treated with more than 2 g/kg body weight DHPN. Adenocarcinomas were induced in 7%, 25%, 86% and 74% of rats treated with 1, 2, 3 and 4 g/kg body weight, respectively. The labelling index studied by 3H-thymidine autoradiography was 0.33% in normal alveoli, 0.49% in bronchiole, 0.62% in focal cell proliferative area, 1.22% in adenoma, 1.70% in tubular adenocarcinoma and 2.81% in papillary adenocarcinoma. Fewer tumours were induced in the thyroid, kidney and sigmoid colon. Only one pancreatic tumour was observed in a rat treated with 3 g DHPN/kg body weight. These results indicate that, in rats, the lung is the organ most responsive to a single treatment with DHPN.
The patient was a 72-year-old woman who had advanced carcinoma of the stomach. She presented massive ascites due to peritonitis carcinomatosa. The cytology of ascites was class V and the CEA level of ascites was elevated. Since renal function was low, we injected 300 mg of carboplatin intraperitoneally 2 times in 8 weeks. The amount of ascites was significantly diminished and the CEA level of ascites was decreased. The result suggested the effectiveness of intraperitoneal injection of carboplatin for the therapy of peritoneal metastasis of gastric cancer.
The satiating effect of intraperitoneal injections of synthetic cholecystokinin octapeptide (CCK-8) was tested in non-deprived and 17 h-deprived male and female Sprague-Dawley rats that were maintained on pelleted diet and offered evaporated milk test meals. At the midpoint of the 12-h diurnal period, 40-160 ng/kg CCK-8 elicited a dose-related decrease in meal size. At midnight, CCK-8's threshold for inhibiting feeding was increased to 80-160 ng/kg in nondeprived and deprived rats, respectively. These doses are 25-50 times less than typically required to significantly decrease food intake after intraperitoneal injection. No CCK-8 dose stimulated nocturnal feeding and no consistent sex difference was observed in CCK-8's effect. Intraperitoneal injection of ng amounts of CCK-8 may mimic a paracrine action of endogenous gut cholecystokinin to signal satiety.
Two experiments were conducted to specify an CS property of intraperitoneally injected odor substance in conditioned odor aversion formation. In experiment 1, three groups of water-restricted rats received one trial of conditioning with intraperitoneal injections of orange-extract (CS) and LiCl(UCS). The CS-UCS intervals of experimental groups were 30 minutes (Group IE-30) and 120 minutes (Group IE-120). In the test trial, Group IE-30 rats showed aversion to the test solution (0.5% orange extract), whereas no significant difference was observed between the control group and Group IE-120. In experiment 2, three groups of rats received one or two or three conditioning trials (Groups E1, E2 and E3, respectively). The CS-UCS interval of all groups was 30 minutes. In the test trial, rats in Groups E2 and E3 consumed less amount of test solution (0.5% orange extract) than the control rats, whereas no significant difference was observed between Group E1 and the control group. These results suggest that the intraperitoneally injected odor substance have CS property on conditioned odor aversion.
The present experiment was undertaken to study the relationship between hemodynamic changes and intracranial hemorrhage induced by intraperitoneal injection of large doses of hypertonic glucose solution in rats. A fifty per cent glucose solution was intraperitoneally injected at a volume of 3.5 ml/100 g b.w. into Wistar rats anesthetized with urethanechloralose. The time span from the start of injection to death was expressed in terms of 100% corrected death time (100% DT) for each rat. Saline that was added to the cerebrospinal fluid in the brain ventricle disappeared gradually from 30% DT up to death. Blood colloid osmotic pressure was slightly elevated temporally 5 minutes (7% DT) after intraperitoneal injection of the glucose solution and returned to the former level 5 minutes later. With regard to hemodynamic changes, a decrease in blood pressure and heart rate began to occur between 5-10% DT. Thereafter, blood pressure and heart rate decreased significantly as compared with the pretreatment period, and the plasma levels of both epinephrine and norepinephrine showed sharply increasing curves as time elapsed after the intraperitoneal injection of the hypertonic glucose solution. It was suggested that the decrease in cerebrospinal fluid and the fall in blood pressure were related to the movement of water from the brain and the flow of body fluid into the hypertonic blood plasma which caused an enlargement of the ventricles due to brain reduction and a change in circulating blood volume. However, questions still remain concerning the mechanisms of the marked increase in plasma catecholamines and bleedings which occurred only in the subarachnoideal space and ventricles.
We investigated the reason for the high mortality we had observed in hypophysectomized-orchidectomized Golden Syrian hamsters that were anesthetized with intraperitoneal (i.p.) injections of chloral hydrate (CH). Intact male Golden Syrian hamsters were injected intraperitoneally with 0.1cc/100g BW of a 35% solution of CH, a 35% solution of sodium chloride, or double-distilled water. Equal numbers of hamsters in each group were injected on the right or left side of the abdomen. Within 10 days, 35% of the CH-injected hamsters were dead or had to be euthanized. Autopsy revealed severe peritonitis and adynamic ileus. CH-injected hamsters that survived gained weight at a rate similar to that of the controls. All surviving hamsters were killed 18 days after the injections. Among the surviving CH-injected hamsters, 84.6% had intra-abdominal adhesions, 61.5% had unilateral testicular atrophy, and 53.8% had a yellowish necrotic mass in the epididymal fat pad (EFP). All the lesions occurred on the side that was injected. The atrophied testes had been rendered cryptorchid due to involvement with intra-abdominal adhesions. In the water-treated controls, there were no abnormalities; whereas, in the saline controls, 75% had a mass in the EFP. Histology of the EFP mass was similar in hamsters injected with CH or hypertonic saline and suggested a diagnosis of fat necrosis. The results suggest that the mortality, the intra-abdominal adhesions, and the unilateral cryptorchidism were caused by a single i.p. injection of CH, but the fat necrosis in the EFP was probably caused by high concentrations of salt. The results further suggest that high concentrations of CH should not be injected intraperitoneally for anesthesia in chronic studies, particularly of the male reproductive system.
The appearances of intraperitoneally injected Amipaque and the absorption rate are described. At 30 min after injection the peritoneal concentration was decreased and the urinary tract began to fill. At one hour, almost all Amipaque had disappeared from the peritoneal cavity and the urinary tract was well demonstrated. As absorption of Amipaque from the gastrointestinal tract is minimal, bowel perforation is thus indicated if, after oral administration, it appears in either the peritoneal cavity or the urinary tract.
The 5-FU concentrations in peripheral blood and portal blood were determined in rats after 5-FU injection via three routes. Rats were given 1 ml of 5-FU (250 mg/kg) via the subphrenic, Douglas or intravenous routes. From comparison of 5-FU concentrations between the intravenous injection group and the intraperitoneal group (subphrenic injection group + Douglas injection group), the intraperitoneal group had a lower concentration than the intravenous one in peripheral blood. The intraperitoneal group showed a higher concentration than the intravenous one in portal blood. The intraperitoneal group was divided into two groups, a subphrenic injection group and a Douglas injection group. Though there was no significant difference between the 2 groups in the 5-FU concentrations in portal blood, the 5-FU concentration of peripheral blood in subphrenic injection group was significantly higher than in the Douglas injection group. It was conceivable that the subphrenic injection group had another absorption route from the abdominal cavity to the peripheral blood. Accordingly, the intraperitoneal injection of the agent may be useful therapy for liver metastasis. However, due care must be given to the injection lesion in the abdominal cavity, the concentration and volume of the agent.
Xenografts (s.c. and i.p.) of human ovarian cancer, shown to express the tumor associated antigen defined by the monoclonal antibody HMFG2, were used to investigate in vivo localization of the radioiodinated antibody after i.p. and i.v. injection. Following i.v. injection, maximum uptake (31.4 +/- 3.5%/g s.c. tumor) was seen in s.c. tumors at 48 h after injection. Tumor:normal tissue ratios increased with time to 240 h. Uptake by ascites and i.p. tumors was less, with a maximum of 10.0 +/- 8%/g ascites reached at 16 h and 11.4 +/- 3.2%/g i.p. tumor at 96 h. After i.p. injection uptake in s.c. xenografts was maximal (14.8 +/- 2.0%/g) at 20 h. For ascites, the i.p. route of administration resulted in high uptake (27.7 +/- 5.8%/g) early (2 h) with an ascites:normal tissue ratio of 69.3 and a specific antibody:nonspecific antibody ratio of 30.8. Except for data at one time point, uptake by i.p. solid tumor was similar to that seen for s.c. tumor. These data strongly suggest that large concentration advantages can be achieved in ascites cells by regional i.p. injection, but that i.p. solid tumor may rely on i.v. delivery of antibody before uptake.