Showing papers on "Intraperitoneal injection published in 1974"

On the Mechanism of the Anti-androgenic Action ofFlutamide (α-α-α-Trifluoro-2-methyl-4'-nitro-m-propionotoluidide)in the Rat

Abstract: The effect of [α-α-α-trifluoro-2- methyl-4'-nitro-m-propionotoluidide], flutamide, on 3H-testosterone and 3H-dihydrotestosterone uptake and metabolism in rat ventral prostate and semial vesicle has been studied and compared to cyproterone acetate. Testosterone-treated castrated rats were given an oral dose of 15 mg/kg of either drug for 3–7 days; neither agent suppressed 3H-testosterone uptake by the tissue at 60 min following an intraperitoneal injection of the labeled steroid given 24 hr after the last dose of drug. Both, however, fully antagonized the effect of testosterone on maintaining prostate and seminal vesicle weights in these rats. In contrast to these results both flutamide and cyproterone acetate, administered p. o. at IS mg/kg/4 days, markedly inhibited 3H-testosterone uptake and retention by prostate and prostate nuclei when labeled androgen was given 3 hr following the last dose of the drug. Similarly, a single dose of these drugs co-administered via ip injection with either 3H-testosteron...

Estrogenic regulation of cytoplasmic receptor populations in estrogen-responsive tissues of the rat.

Abstract: Female castrate rats were sacrificed at intervals following a single intraperitoneal injection of either 1, 5 or 10 µg of 17β-estradiol. Maximal depletion of cytoplasmic receptors occurred in uterus, anterior pituitary and hypothalamus at 1 hr. By 10 hr postinjection, tissue cytosols had regained greater than 50% of initial receptor capacities. The replenishment process was synchronous in all three tissues. Concomitant administration of 10 µg of 17β-estradiol and 1 mg of cycloheximide inhibited replenishment, but did not alter initial depletion; this response was not attributable to a direct effect of cycloheximide on the depletion-replenishment process. Intact and 2-week hypophysectomized rats had levels of receptor comparable to female castrate animals. Depletion following 17β-estradiol was similar, but significantly greater 15-hr replenishment was observed as compared to castrate. Administration of 17α-estradiol only slightly depleted receptor levels, but did result in the cycloheximide-sensitive appea...

Stimulation of DNA synthesis in mouse lung following intraperitoneal injection of butylated hydroxytoluene.

Abstract: SummaryMale Swiss-Webster mice were injected ip with 400 mg/kg of the antioxidant buty-lated hydroxytoluene (BHT). Between 2 and 5 days after BHT, there was a marked increase in the incorporation of thymidine into pulmonary DNA; 7 and 9 days after BHT, incorporation of thymidine fell towards values found in control animals. The increased incorporation of thymidine was accompanied by a net and significant increase in total lung weight and a persistent elevation of total lung DNA. Butylated hydroxytoluene did not stimulate DNA synthesis in liver, kidney, spleen, or gastrointestinal tract. Butylated hydroxytoluene could be used as a tool to study the biochemical events leading to or accompanying stimulated DNA synthesis and cell growth in lung.

Persistence of Cadmium-Induced Metabolic Changes in Liver and Kidney

Abstract: Daily intraperitoneal injection of cadmium chloride (1 milligram per kilogram) for 45 days enhanced gluconeogenesis as evidenced by significant increases in the activities of liver and kidney cortex pyruvate carboxylase, phosphopyruvate carboxylase, hexosediphosphatase, and glucose-6-phosphatase, the quartet of key, rate-limiting enzymes involved in the biotransformation of noncarbohydrate precursors into glucose. Whereas cadmium treatment decreased the level of hepatic glycogen, the concentration of blood glucose and urea was significantly elevated by this heavy metal. Discontinuation of the heavy metal treatment for 28 days, in rats previously injected with cadmium for 45 days, failed to restore the observed biochemical alterations in hepatic and renal carbohydrate metabolism to control values. Evidence indicates that cadmium augments the glucose-synthesizing capacity of liver and kidney cortex and that various metabolic changes persist even after a 4-week period of withdrawal from exposure to the heavy metal.

Tumour growth, phagocytic activity and antibody response in Corynebacterium parvum-treated mice.

Abstract: Serum from both normal and T cell-deprived female adult CBA mice shows a background titre of antibody to Corynebacterium parvum of about 2–4 log2 units by a latex agglutination test. Intraperitoneal injection of C. parvum causes a marked rise in titre which reaches its peak after about a month, and a second injection at that time evokes a further response. Treatment with mercaptoethanol reduces the background titre, and also the titre 1–3 weeks after immunization by 1–2 log units. Subcutaneous injection of C. parvum on the other hand evokes little or no antibody response. Both the antitumour effect of C. parvum, and its effect on clearance of colloidal carbon from the blood stream, can occur in the presence of high levels of antibody directed against the organism. Theoretical and possible therapeutic implications of these findings are discussed.

In vivo effect of estradiol benzoate on the accumulation of adenosine 3',5'-cyclic monophosphate in the rat hypothalamus.

Abstract: The effect of an intraperitoneal injection of estradiol benzoate (EB) upon cyclic AMP accumulation in the hypothalamus of 21-day-old rats was studied. Clomiphene citrate administration prior to EB neu

Effect of endotoxin on tumor resistance in mice.

Abstract: As reported earlier, an intraperitoneal injection of 1 μg of endotoxin (ET) from Serratia marcescens rendered mice resistant against the nonspecific mouse ascites tumor TA3-Ha upon challenge 24 h after pretreatment with ET. Further studies were aimed at the elaboration of conditions which achieved maximal resistance. It appears that (i) a 10-μg dose of ET was approximately the optimal dose for protection; (ii) pretreatment with ET 3 to 0 days prior to tumor challenge gave best protection; and (iii) the intravenous injection of ET showed a lower protection against the tumor than intraperitoneal application. Studies on the mechanism of ET protection indicate that (i) ET does not have a direct cytotoxic effect on tumor cells; (ii) normal spleen cells exposed to ET in vitro can adoptively transfer protection against tumor; and (iii) spleen cells activated in vivo by intravenous injection of ET can adoptively transfer protection. The possible involvement of mononuclear cells is discussed.

Influence of scretin and pentagastrin on the circadian rhythm of cell proliferation in the intestinal mucosa in rats.

Abstract: The effects of Secretin (3.5 U/100 g) and Pentagastrin (25 μg/l00 g) on cell renewal in jejunal mucosa was studied in male Wistar rats. The labeling index (LI), mitotic index (MI), and histogram of the distribution of labeled cells were measured at 4-hour intervals during 24 h after intraperitoneal injection of hormones and compared with results obtained in control animals. DNA label was obtained by injection of tritiated thymidine (70 μCi/100 g) 30 min before sacrificing the animals. The proliferation of intestinal cells in rats was marked by a circadian rhythm with a nocturnal peak of DNA synthesis. After Pentagastrin, the LI remained high for 16,20, and 24 h after injection, during the time the control levels diminished in the circadian rhythm. The normal MI and the enlargement of the zone of proliferation support the hypothesis of a stimulating effect of gastrin on intestinal cell renewal. After Secretin, the LI peak of the cycle was suppressed and the MI decreased, indicating an inhibiting effect of Secretin on intestinal cell renewal. Secretin and gastrin act as trophic factors on intestinal mucosa and produce opposite effects on cell proliferation.

Studies on a new antiviral antibiotic, 9-methylstreptimidone. I. Physicochemical and biological properties.

Abstract: A new antiviral agent which inhibits the growth of poliovirus, vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV) was isolated from the culture filtrate of a Streptomyces and shown to be 3-(5, 7-dimethyl-4-oxo-2-hydroxy-6, 8-decadienyl)-glutarimide. The actue LD50 of the antibiotic in mice by intraperitoneal injection was 280 mg/kg. Serum specimens taken 10 minutes after intraperitoneal injection of 2.5 mg/kg to mice inhibited the growth of poliovirus.

Some Physiological and Biochemical Effects of a Coxiella burneti Lipopolysaccharide Preparation on Guinea Pigs

Abstract: A lipopolysaccharide obtained in a dialyzed phenol extract from the rickettsia Coxiella burneti produced the following effects in guinea pigs after intraperitoneal injection: hyperthermia, loss of body weight, increased liver weight and concomitant lipid infiltration, elevated levels of hepatic and plasma cortisol, increased incorporation of [3H]orotic acid into hepatic 28S and 18S ribosomal ribonucleic acid, increased incorporation of 14C-labeled amino acids into liver and plasma protein, and leukocytosis. Most of these events also occur during infection of guinea pigs with C. burneti, and a causal relationship between the rickettsial lipopolysaccharide and the biochemical changes that occur during Q fever is suggested.

Fine structure of rat islet cell tumors induced by streptozotocin and nicotinamide.

Abstract: Young male Holtzman rats were injected intravenously with 50 mg/kg of Streptozotocin, preceded and followed by a single intraperitoneal injection of 350 mg/kg of nicotinamide, according to the method of Rakieten et al. [16]. After 245 to 323 days, 27 pancreatic islet cell tumors measuring up to 0.6 cm were demonstrable in 20 of 41 rats so treated; they were solitary in 15 and multiple (two or three neoplasms each) in five animals. It was not possible to distinguish between tumor-bearing and tumor-free rats on the basis of periodic blood sugar determinations and serum insulin assays. Mean insulin concentration in grossly tumor-free pancreatic specimens was 0.661 units of insulin/g of wet tissue, but amounted to 5.385 units/g in specimens containing tumor. The islet cell tumors were rounded and well delineated. They were located in all parts of the pancreas. In general, their cells stained deeply with aldehyde-fuchsin. Ultra-structurally, most tumors consisted of well granulated B cells. A or D cells were not encountered while occasional EC cells were identified. Nucleoli were frequently prominent. Some necrotic B cells and others with few or unusually small secretory granules were present. Extravasated erythrocytes as well as hemosiderin deposits were seen in many tumors, and tumor cell particles were occasionally noted within the lumina of capillaries. Distant metastases were not demonstrable in this group of animals.

The different susceptibility of rat liver lobes to carbon tetrachloride and dimethylnitrosamine.

Abstract: The extent of liver damage in rats dosed with carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN), by intragastric or intraperitoneal injection, has been compared in the different lobes. The level of activity of DMN-demethylase in the lobes has also been measured as an index of the activity of the microsomal enzymes. DMN-demethylase activity was greater in the left and left median lobes than in the right and right median lobes. The extent of liver damage (disruption of the basophilic bodies and necrosis) was greater in the right than in the left lobes of animals dosed with CCl4 but was greater in the left lobes of animals given DMN. The route of injection made no difference. The distribution of liver damage may be explained by the distribution of microsomal enzymes.

STUDIES ON FLAVONOID METABOLISM: Excretion of m-Hydroxyphenylhydracrylic Acid from (+)-Catechinin the Monkey (Macaca iris sp.)

Abstract: Oral administration or intraperitoneal injection of (+)-catechin to monkeys resulted in the excretion of 10 phenolic metabolites. The principal phenolic acid metabolite is m -hydroxyphenylhydracrylic acid and the major lactone metabolite is δ-(3-hydroxyphenyl)-γ-valerolactone. The m -hydroxyphenylhydracrylic acid was shown to arise from β-hydroxylation of m -hydroxyphenylpropionic acid which is one of the metabolites of (+)-catechin. The metabolites of (+)-catechin are excreted both in the free and conjugated form. m -Hydroxyphenylhydracrylic acid and† -(3-hydroxyphenyl)-γ-valerolactone amounted to about 4.3 and 7.6% of the administered dose. respectively. Oral administration and intraperitoneal injection of (+)-[U- 14 C]catechin resulted in the urinary excretion of 53.5 and 50.2% of the dose, respectively. The radioactivity detected in the feces was between 0.8 and 2.2% of the dose. The species variation in the metabolism of (+)-catechin is discussed.

Alpha-amanitin inhibition of mouse brain form II ribonucleic acid polymerase and passive avoidance retention.

Abstract: Injection of α-amanitin into a cerebral ventricle reduced the ability of male mice to retain a passive avoidance response without affecting spontaneous locomotor activity or performance of a previously learned task. α-Amanitin inhibited the brain form II DNA-dependent RNA polymerase in a dose-dependent manner up to 10 µg, at which dose a maximum of 98% inhibition was observed as determined by assay of brain nuclei at the time of training. The effect observed on passive avoidance retention is only seen at maximal (98%) inhibition. Furthermore, the inhibition of brain form II polymerase is transient, indicating that α-amanitin is effective in vivo only when virtually 100% inhibition of this enzyme is attained. The liver form II polymerase was also inhibited after cerebroventricular injection, indicating that a significant amount of the α-amanitin reached peripheral circulation. A 50% inhibition of liver form II polymerase was measured within 15 min. However, intraperitoneal injection of 10 µg of α-amanitin did not produce significant inhibition of brain form II polymerase, and retention of a passive avoidance response was not affected.

Selective inhibition of dopamine-beta-hydroxylase in the peripheral tissues by 5-dimethyldithiocarbamylpicolinic acid; its effect on stress-induced ulcer, ethanol-induced sleep and blood pressure.

Abstract: Administration of 5-dimethyldithiocarbamylpicolinic acid (YP-279), an inhibitor of dopamine- β-hydroxylase, caused selective reduction of peripheral norepinephrine (NE) biosynthesis and reduced the blood pressure of spontaneously hypertensive rats, as well as normotensive rats, but had no effect on brain NE biosynthesis. YP-279, which does not appear to cross the blood-brain barrier, did not affect either stress-induced gastric ulcer or ethanol-induced sleeping time, both of which are thought to he mediated through the central nervous system. Evidence that YP-279 is a selective inhibitor of the peripheral dopamine-β-hydroxylase is 1) that the conversion of 3H-dopamine into 3H-NE in rat brains was not inhibited by intraperitoneal injection of this compound, but the conversion of 3H-dopamine into 3H-NE in rat hearts was effectively inhibited and 2) that this inhibitor could not be detected in the brain after its intraperitoneal administration, but could be detected in other tissues. In contrast, 5-butylpicolinic acid and its derivatives (analog of YP-279), which also inhibit dopamine-β-hydroxylase, that do pass the bloodbrain barrier exhibited all of the positive effects indicated above as well as abilities to prevent stress-induced gastric ulcers and to prolong ethanol-induced sleep. 5-Butylpicolinic acid and its derivatives, except for YP-279, were found in brain and peripheral tissues. They also inhibited the conversion of 3H-dopamine into 3H-NE in the brain as well as in other tissues.

Protection of rats against the hepatotoxic effect of paracetamol.

Abstract: In view of increasing knowledge of the mechanism of production of hepatic damage by paracetamol, and the results of recent studies suggesting a beneficial effect from cysteamine administered soon after an overdose, studies were carried out in the rat on a number of possibly protective agents, using oral paracetamol in a dose of 2·5 g/kg body weight. Histological evidence of liver damage was reproducibly obtained with corresponding reductions in the levels of cytochrome P450. This was completely prevented by prior oral administration of cysteamine in a dose of 300 mg/kg body weight. The levels of cytochrome P450 were also maintained following an intraperitoneal injection of α-tocopherol (400 mg/kg body weight) but the effect on the histological evidence of liver damage was less. The administration of glutathione, propranolol and thioctic acid did not prevent the liver damage, although with these agents—except glutathione—the number of wedge shaped areas of necrosis (infarcts) in the liver was reduced.