Showing papers on "Intraperitoneal injection published in 1985"

Regional cerebral blood flow decreases during hyperglycemia

Abstract: The presence of hyperglycemia before brain ischemia increases stroke-related morbidity and mortality in experimental animals and humans. However, little is known of the effect of hyperglycemia on regional cerebral blood flow (rCBF). Acute hyperglycemia was induced in awake but restrained rats by intraperitoneal injection of 50% D-glucose. Regional flow was determined using [14C]iodoantipyrine and quantitative autoradiography. Elevation of plasma glucose from 11 to 39 mM was associated with a 24% reduction in rCBF when compared with controls that received normal saline. Intraperitoneal D-mannitol produced an elevation of plasma osmolality equivalent to that observed with glucose. However, rCBF was only reduced by 10%. Hyperglycemia appears to produce a global decrease in rCBF in awake rats that cannot be completely explained by the attendant increase in plasma osmolality. If a similar influence is present during brain ischemia, hyperglycemia could extend areas of critical flow limitation.

Exchange of Macromolecules Between Peritoneal Cavity and Plasma

Abstract: The exchange of fluorescein isothiocyanate-labeled dextrans ranging in weight-averaged molecular weight from 19,400 to 160,000 and 125I-bovine serum albumin (BSA) between dialysis fluid (5% BSA in Krebs-Ringer solution) in the peritoneal cavity and the plasma was studied in anesthetized female Sprague-Dawley rats. Plasma and peritoneal samples were collected for 3-4 h after either 1) an intraperitoneal injection of dialysis fluid with tracer or 2) an intravenous injection of tracer material simultaneously with an intraperitoneal injection of dialysis solution without tracer. Analysis of the data by means of a mathematical model of the transport process suggests a functional asymmetry in transport of large molecules across the blood capillary wall. Substances injected intravenously have a net transport from the blood capillaries to the peritoneal cavity. Substances of molecular weight greater than or equal to 39,000 transport from the cavity to the plasma via peritoneal lymphatics; 19,400 molecular-weight dextran transports from the cavity to the plasma primarily via lymphatics with some blood capillary uptake. Tissue diffusivities and capillary mass transport coefficients are derived for the substances tested.

In vivo treatment of rats with monoclonal anti-T-cell antibodies. Immunohistochemical and functional analysis in normal rats and in experimental allergic neuritis.

Abstract: The effects of intraperitoneal injection of monoclonal anti-rat T-lymphocyte antibodies were evaluated immunohistochemically and functionally in normal rats and in rats with experimental allergic neuritis. In the normal animals a single injection of OX8 antibodies, reactive with suppressor/cytotoxic T cells, completely eliminated OX8-reactive cells from peripheral lymphoid organs and from circulation, whereas the ‘pan’ T-cell-reactive W3/13 antibodies and the helper T-cell-reactive W3/25 antibodies only caused a partial elimination of their respective target cells. Injection of the W3/13 and W3/25 antibodies but not of OX8 antibodies led to a diminished responsiveness to allogeneic stimulation in vitro for spleen cells obtained from the treated rats, whereas the OX8 injection caused a complete elimination of the in vitro cytotoxic response to allogeneic cells in the mixed lymphocyte reaction-activated spleen cell population. When Lewis rats were injected with peripheral nerve myelin and Freund's adjuvant for the induction of EAN, treatment with W3/13 antibodies completely prevented the onset of disease, whereas treatment with the OX8 antibodies exaggerated the disease symptoms.

Anti-tumor effect of inflammatory neutrophils: characteristics of in vivo generation and in vitro tumor cell lysis.

Abstract: Inflammatory neutrophils elicited by intraperitoneal injection of Corynebacterium parvum, thioglycollate or proteose peptone were capable of lysing different murine and human tumor targets in a short-term chromium-release assay. A single-cell cytotoxicity assay, which evaluated effector-target cell interactions at the single-cell level, confirmed a PMN-mediated tumor-lytic effect. Optimal lysis was achieved by PMNs obtained 6 hr after injection of C. parvum and 16 hr after injection of thioglycollate. In vitro, loss of tumor cell membrane integrity occurred extremely rapidly following conjugation with inflammatory PMNs (beginning within 15 min of the binding step). By 45 min, the lytic event was completed. Addition of catalase or superoxide dismutase to the cytotoxicity assays prevented tumor lysis in a concentration-dependent fashion, indicating that hydrogen peroxide and superoxide, products of the PMN respiratory burst, are mediators of the lytic reaction.

Cyclophosphamide-Induced Depression of the Antioxidant Defense Mechanisms of the Lung

Abstract: Cyclophosphamide causes lung toxicity in a wide variety of animals, including humans. Recent evidence suggests that oxygen (O2) potentiates cyclophosphamide-induced pulmonary injury. We hypothesized that cyclophosphamide or one of its toxic metabolites, acrolein, may potentiate O2 toxicity by depressing lung antioxidant defense mechanisms. To test this, we gave rats cyclophosphamide (100 mg/kg), acrolein (5 mg/kg), or a vehicle (control) in a single intraperitoneal injection and then killed them during a 5-day study period. Excised lungs were analyzed for reduced glutathione (GSH) content, glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSH-R), glutathione peroxidase (GSH-P), and superoxide dismutase (SOD) activities. In the lungs of cyclophosphamide-treated rats, GSH content was increased 48% (P less than 0.001) on day 2 but progressively decreased to 50% of control values (P less than 0.001) on day 5. Significant reductions (P less than 0.005) in G6PD, GSH-R, and GSH-P activities occurred on days 1-5, and SOD activity was significantly decreased (P less than 0.005) on days 4 and 5 by cyclophosphamide. In acrolein-treated rats, GSH content and GSH-R, GSH-P, and SOD activities were indistinguishable from those in controls. However, G6PD was increased (35-38%) on days 2 and 3 but returned to control values thereafter. To assess whether the cyclophosphamide-induced reduction in lung antioxidant defenses increased susceptibility to acute O2 toxicity, we gave a separate group of rats cyclophosphamide, acrolein, or vehicle, and 4 days later exposed them to 100% O2 or air at 1 atmosphere absolute. All cyclophosphamide-, acrolein-, and vehicle-treated rats survived 60 h air exposure, and all vehicle-treated rats exposed to 100% O2 survived. In contrast, all of the cyclophosphamide-treated rats exposed to 100% O2 died (P less than 0.05) within 40 h. Acrolein had no effect on survival in 100% O2. These results indicate that cyclophosphamide, but not acrolein, depresses lung antioxidant defense mechanisms, which may be responsible for increased mortality from O2 toxicity in cyclophosphamide-treated animals.

Vanadium exposure enhances lipid peroxidation in the kidney of rats and mice.

Abstract: Vanadium (V) as sodium orthovanadate induces an increase in lipid peroxidation in the kidneys after a single subcutaneous or intraperitoneal injection to rats or mice. The rate of malondialdehyde (MDA) formation, an index of lipid peroxidation, by-kidney homogenates increased by more than 100% 1 h after injection. Chronic exposure of rats to vanadium sulfate, initially through maternal milk and later in the drinking water, resulted after 10 weeks in a significant increase in MDA formation by kidney but not by other tissues, in both acute and chronic studies in rats and mice, no significant increase in lipid peroxidation by V treatment was detected in brain, heart, lung, spleen, or liver. In mice, administration of ascorbate prior to acute exposure to V diminished both toxicity, i.e., respiratory depression and limb paralysis, and the formation of MDA in kidney.

Long-term consequences of cis-platinum-induced renal injury: a structural and functional study.

Abstract: Previous studies have shown that a single dose of the antitumor drug, cis-platinum, causes renal cyst formation in rats 1-6 months after drug injection. This observation led to a further evaluation of the long-term effects of cis-platinum on the kidney of the rat. Fisher 344 rats (N = 13) were given either a single intraperitoneal injection of cis-platinum (6 mg/kg body weight) or saline (control) and 15 months later renal function and pathology were assessed. The glomerular filtration rate and urinary osmolality in the cis-platinum-treated rats at 15 months were significantly reduced compared to controls, 520 +/- 59 microliter/min/gm kidney weight versus 799 +/- 100 (P less than .05) and 871 +/- 194 mOsm/kg H2O versus 1471 +/- 162 (P less than .05), respectively. Renal injury was less marked and of a more chronic type than to that originally described 6 months after cis-platinum. Morphometric evaluation of renal injury revealed cis-platinum-treated rats had greater numbers of abnormal proximal tubules (atrophic or hyperplastic) when compared to control rats. Glomerular sclerosis and interstitial fibrosis were also more prevalent in the animals injected with cis-platinum. In the inner stripe of the outer medulla, numerous markedly dilated tubules filled with hyaline casts and lined by simple squamous cells were present. To assess why cis-platinum exerts a chronic effect on the kidney, total platinum levels were measured in different regions of the kidney as a function of time after drug injection. Platinum levels were significantly elevated in the cortex, outer and inner stripe regions, and in the inner medulla for as long as 1 month after cis-platinum treatment. By 2 months, however, the values were no greater than controls. In summary, cis-platinum exerts a significant long-term chronic effect on the structure and function of the rat kidney.

Biodistribution of the radioprotective drug 35S-labeled 3-amino-2-hydroxypropyl phosphorothioate (WR77913).

Abstract: 3-Amino-2-hydroxypropyl phosphorothioate (WR77913), a less toxic phosphorothioate radioprotector than WR2721, has been labeled with 35S. The biodistribution of a radioprotective dose of 800 mg/kg was determined in C3H mice bearing RIF-1 tumors as a function of time after intraperitoneal injection and was expressed as percentage injected dose/gram (% ID/g). Levels of 35S in the blood peaked 10 min after injection, and radioactivity in most tissues was highest at 15 min. Label in most tissues declined markedly between 15 and 60 min, but in gut, salivary glands, tumor, and brain, the levels of radioactivity remained quite stable over 1 hr. At 30 min after injection the highest levels of labeled drug were found in submandibular salivary glands, gut, and kidney, with the lowest level in brain. Tumors had approximately the same amount of label as blood, muscle, skin, and esophagus. Two principal differences between the distribution of label from WR77913 and WR2721 were defined. Although blood levels of 35S-WR2721 also peaked 10 min after injection, the 10-min blood levels achieved for WR77913 were more than fourfold greater than those attained by WR2721. Maximum levels of WR2721 occurred in most tissues 30 to 60 min after administration of the drug, compared to 15 min for WR77913. The basis for these differences remains to be determined, but these results suggest that the optimum interval between administration of WR77913 and irradiation may be shorter than for WR2721.

Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans.

Abstract: Mice receiving a single intraperitoneal injection of amphotericin B showed increased resistance to subsequent challenge with either Candida albicans or Staphylococcus aureus. This enhancement of resistance was obvious in terms of both survival criteria and clearance of the intravenously injected organism from different organs. The protective effect of amphotericin B was conditioned by dose, time of drug administration, and size of yeast or bacterial inoculum and was reversed by cyclophosphamide. Effector cells from mice treated with amphotericin B displayed enhanced fungicidal activity in vitro as measured in a short-term 51Cr release assay. Macrophages from intact animals exposed in vitro to amphotericin B also acquired strong candidacidal reactivity.

Influences of catecholamines on growth hormone release in female goldfish, Carassius auratus.

Abstract: The influence of catecholamines on growth hormone (GH) release in female goldfish was investigated by monitoring serum GH levels following injections of drugs known to alter catecholamine synthesis and neural activities. Intraperitoneal (i.p.) injection of 6-hydroxydopamine, a catecholaminergic neurotoxin, or alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, decreased serum GH levels. Intraperitoneal injection of L-beta-dihydroxyphenylalanine (L-dopa) increased serum GH concentrations in a dose-dependent manner. The L-dopa-induced increase in serum GH was potentiated by i.p. injection of carbidopa, which would increase the availability of L-dopa to brain tissues by blocking the peripheral conversion of L-dopa to dopamine (DA). These results suggest that L-dopa or one of its catecholamine metabolites acts centrally to increase GH release. Intraventricular (i.v.t.) injection of DA and i.p. injection of apomorphine, a DA agonist that crosses the blood-brain barrier, increased serum GH. Intraperitoneal injection of DA did not alter circulating GH levels in normal fish or fish bearing preoptic lesions that abolish an inhibitory hypothalamic influence on GH release; however, DA increased serum GH in fish which had their blood-brain barrier destroyed by sham operation procedures. These results indicate that DA acts centrally to stimulate GH secretion, possibly by inhibiting the release and/or synthesis of GH release-inhibitory factor. Serum GH concentrations were decreased in a dose-dependent manner by i.p. injection of norepinephrine (NE), whereas i.v.t. injection of NE did not alter serum GH levels. These results indicate that NE acts outside of the blood-brain barrier to decrease serum GH levels in the goldfish, possibly by directly influencing pituitary GH cells.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo and in vitro studies on the release of cortisol from interrenal tissue in trout. I. Effects of ACTH and prostaglandins.

Abstract: The secretion of cortisol from the interrenal tissue in trout Salmo gairdnerii was studied in vivo and by an in vitro superfusion method in relation to the effect of adrenocorticotropic hormone (ACTH), prostaglandins (PGE1, PGF2 alpha) and prostaglandin inhibitors. The experiments were performed between April and July. In control, uninjected animals, circulating cortisol was 206 +/- 24 ng/ml. At 24 h following the intraperitoneal injection of indomethacin, dexamethasone, or both, the levels were reduced to 84 +/- 10, 43 +/- 20 and 63 +/- 11 ng/ml respectively. In control animals receiving solvent (ethanol), the value was 190 +/- 30. With longer term duration (72 h) the levels of plasma cortisol following injection of indomethacin, dexamethasone and both drugs together were 120 +/- 29, 120 +/- 10 and 37 +/- 8 respectively. On the contrary, no significant change was produced by prostaglandins. In vitro release of cortisol from superfused head kidneys (which contain the interrenal tissue of teleosts) decreased gradually with time and reached a minimum after 50 min. Addition of ACTH or of PGE1 to the medium induced an immediate, dose dependent increase in cortisol output which reached a maximum after 15-30 min. On the contrary, PGE2 alpha or indomethacin did not modify cortisol release. These results show that cortisol production in trout, which is controlled by ACTH as in other vertebrates, is also under the influence of other hormonal substances acting on the adenyl-cyclase system.

Genetically determined differences in acute responses to diisopropylfluorophosphate.

Abstract: The acute effects of diisopropylfluorophosphate (DFP) were assessed in DBA/2Ibg, C57BL/6Ibg and C3H/2Ibg mice. The DFP was administered by intraperitoneal injection in saline. Brain acetylcholinesterase (AChE) activity was maximally inhibited within 5 min after injection. All mice showed signs of organophosphate intoxication including salivation, lacrimation, diarrhea, respiratory distress, tremor and, at high doses, seizures. The C57BL mice were most susceptible to these effects of DFP. The LD 30 values for DFP were 8.0, 7.6, and 6.8 mg/kg for male DBA, C3H, and C57BL mice, respectively. The LD 50 values for females were nearly the same. Body temperature and brain AChE activity decreased in a dose-dependent manner following injections of DFP of 3.17, 4.22, 5.28, and 6.33 mg/kg. Maximum temperature depression occurred 2 hours after DFP administration; by 24 hours temperatures had returned to normal except for C57BL mice treated with the highest dose of DFP. The C57BL strain was most susceptible to the DFP-induced hypothermia, the C3H strain was the most resistant, and the DBA strain was intermediate. Maximum temperature depression and residual AChE activity, as measured 24 hours after injection, were linearly related. These strain differences do not seem to be explained easily by a differential inhibition of AChE activity.

A Paracoccidioides brasiliensis polysaccharide having granuloma-inducing, toxic and macrophage-stimulating activity.

Abstract: The occurrence of a polysaccharide fraction of Paracoccidioides brasiliensis cell wall with toxic, granuloma-inducing and macrophage-stimulating activities was demonstrated. After fractionation of the lipid-extracted wall with 1 M-NaOH, three fractions were obtained: (1) an alkaliinsoluble fraction: (2) an alkali-soluble, acid-insoluble fraction and (3) an alkali-soluble, acid-soluble fraction. When the three fractions were injected into mice only fraction (1) was able to induce chronic lung inflammation, causing a marked loss in body weight and death at a dose of 6 mg per animal. Analysis of the stimulation of peritoneal macrophages of mice (measured by cell spreading on glass) after intraperitoneal injection of fraction 1 showed that 75% of the cells were able to spread even 20 d after inoculation.

Dissociation between pancreatic islet blood flow and insulin release in the rat.

Abstract: The blood flow to the pancreatic islets was estimated with the aid of microspheres in fed or starved (72 h) rats. The total pancreatic blood flow (PBF) in fed animals was 0.55 +/- 0.04 ml X min-1 X g pancreas and in the starved animals 0.30 +/- 0.04 ml X min-1 X g pancreas (P less than 0.001), and the corresponding islet blood flow (IBF) 82.0 +/- 12.4 and 50.5 +/- 9.7 microliter min-1 X g pancreas respectively (P greater than 0.05). Intraperitoneal injection of 2 ml of a 30% glucose solution caused a marked increase in IBF in both fed (P less than 0.05) and starved (P less than 0.01) animals to approximately the same level. The circulating insulin concentration remained unaffected by glucose in the starved rats but increased (P less than 0.001) in the fed rats, indicating that insulin release does not necessarily rise in parallel with an elevated IBF. Intraperitoneal injection of 2 ml of a 30% solution of mannoheptulose, an inhibitor of islet glucose metabolism, decreased the serum insulin concentrations although the serum glucose concentrations rose significantly in both fed (P less than 0.001) and starved (P less than 0.001) animals. This treatment, however, caused both IBF and PBF to increase significantly in both groups. The data support the view that islet blood flow is not necessarily related to the metabolic status of the islet cells or to the insulin release.

Physiological changes in the activities of extramitochondrial acetyl-CoA hydrolase in the liver of rats under various metabolic conditions

Abstract: Significant increase in the activity of an acetyl-CoA hydrolase (ATP-stimulated, ADP-inhibited enzyme) in the supernatant fraction of rat liver was observed after 44-68 h of starvation (about 2-fold), and in the early stage of diabetes (about 1.6-fold), but not in the chronic stage of diabetes. The increased enzymatic activity in starved rats returned to the control level within 20 h when the animals were given laboratory chow, but not when they were given fat-free diet with a high carbohydrate content, and the enzyme activity was increased by the latter diet containing 1% thyroid powder. A single intraperitoneal injection of 3,3'5-triiodo-L-thyronine or 3,3',5,5'-tetraiodo-L-thyronine resulted in twice the normal enzyme activity two days later, and conversely 7 days after thyroidectomy, the enzyme activity was about 60% of the control level. A single subcutaneous injection of alpha-(p-chlorophenoxy)isobutyric acid, a hypolipidemic drug, doubled the enzyme activity in euthyroid rats, but not in thyroidectomized rats. Of the various tissues tested besides the liver, only the kidney had detectable ATP-stimulated and ADP-inhibited enzyme activity (5% of the activity in liver cytosol). The kidney enzyme had similar kinetic and immunochemical properties to the liver enzyme. Changes in the enzyme activity in the liver in various states were closely related to the amount of enzyme present, judging from results obtained by enzyme-linked immunosorbent assay. The physiological role of this enzyme (which hydrolyzes acetyl-CoA to acetate and CoASH) may be in maintenance of the cytosolic acetyl-CoA concentration and CoASH pool for both fatty acid synthesis and oxidation.

Inhibition by 2-Bromo-α-Ergocriptine and Tamoxifen of the Growth of an Estrogen-dependent Transplantable Pituitary Tumor (MtT/F84) in F344 Rats

Abstract: A new transplantable pituitary tumor, designated MtT/F84, was induced in estrogenized female F344 rats and has been serially passaged in 17β-estradiol-treated females. It grew well in rats treated with estrone, 17β-estradiol, or estriol but not in intact females or in rats given progesterone or testosterone. The growth of MtT/F84 in rats grafted with up to 1.6 × 106 tumor cells and given 17β-estradiol was inhibited by orally administered high dose bromocriptine (37.5 mg/kg in food) or by intraperitoneal injection of tamoxifen citrate but was not inhibited by low dose bromocriptine (3.75 mg/kg in food). The tumors grown in intact females contain high amounts of estrogen receptor, and they were greatly reduced in the tumors grown either in 17β-estradiol or 17β-estradiol-plus-tamoxifen loaded rats. However, administration of bromocriptine resulted in estrogen receptor levels significantly higher than those of tumors grown in 17β-estradiol. The existence of dopamine receptor was also confirmed. Growth inhibition of MtT/F84 either by high dose bromocriptine or by tamoxifen may be a direct action and may be an estrogen and dopamine receptor-mediated phenomenon.

Acute cytogenetic effects of potassium bromate on rat bone marrow cells in vivo

Abstract: The acute cytogenetic effects of potassium bromate (KBrO3) on rat bone marrow cells in vivo were studied The incidence of chromosome aberrations in bone marrow cells increased rapidly, reaching a maximum level 12 h after intraperitoneal injection and decreased within 24 h Dose-response relationships were obtained for both intraperitoneal and oral administrations

In vivo effects of follicle-stimulating hormone on testicular macrophages.

Abstract: The effect of an intraperitoneal injection of various hormones on the incorporation of amino acids and uridine into acid-precipitable material by subsequently isolated testicular macrophages was investigated. It was found that treatment with follicle-stimulating hormone (FSH), but not luteinizing hormone (LH) or insulin, significantly increased incorporation of amino acids into secreted (but not cellular) protein and uridine incorporation into cellular RNA in a dose-dependent manner. Maximal responsiveness was observed at a dose of 50 micrograms of the hormone. These studies demonstrate that FSH has an action on testicular macrophages in vivo.

Alteration of Amino Acid Metabolism in Epileptogenic Mice by Elevation of Brain Pyridoxal Phosphate

Abstract: A single intraperitoneal injection of pyridoxal-5'-phosphate (PLP) in a species of mouse, DBA/2J, that is normally susceptible to sound-induced convulsion exacerbated its epileptic condition. The effect of injection was most pronounced about 30 min after the administration and subsided gradually within the following 4 h. Correlated with this increased seizure susceptibility were enhanced levels of synaptosomal aspartate and glutamate, and a diminished gamma-aminobutyric acid (GABA) level. The concentrations of nonneuroactive amino acids remained unchanged. When stimulated with veratrine, synaptosomes prepared from PLP-injected mice showed an increased release of aspartate and glutamate and a decreased release of GABA compared to those prepared from control mice. The activity of glutamate decarboxylase in the brains of PLP-treated mice was lowered, whereas the activity of GABA-transaminase was enhanced. Finally, the epileptic condition of DBA mice could be ameliorated by maintenance on a diet composed of vitamin B6-deficient feed and cellulose.