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Characteristics of xenograft rejection. I. Augmented cytotoxicity of peritoneal T cells after intraperitoneal injection of booster antigen and/or proteose peptone.

Cytotoxic activity was detected by the 51 CR-release test in peritoneal exudate (PE) cells of mice immunized with rat lymphocytes 5 days previously, but not in their spleen or lymph node cells. This activity appeared to be exerted by cytotoxic T cells, which had the same characteristics as those for allogeneic systems in respect to antigen specificity and time course. An intraperitoneal booster with rat lymphocytes 2 days before the assay effectively enhanced the cytotoxic activity of PE cells. When mice were immunized with rat lymphocytes subcutaneously or intravenously, cytotoxic activity was scarcely detected in PE cells. However, significant activity was detected in PE cells when the immunized mice were injected intraperitoneally with proteose peptone 2 days before the assay.

Animals↗

Estradiol-mediated increases in the anorexia induced by intraperitoneal injection of bacterial lipopolysaccharide in female rats.

Lipopolysaccharide (LPS) derived from the cell walls of gram-negative bacteria causes a robust acute phase response (APR) that includes fever, anorexia, and many other elements. Because immune system function, including some models of illness anorexia, is sexually differentiated, we investigated the sexual differentiation of the anorexia induced by intraperitoneal LPS injections in rats. Cycling female Long-Evans rats tested either during diestrus or estrus ate less following 6.25 microg/kg LPS than did intact males. Following 12.5 microg/kg LPS, females in estrus ate less than either females during diestrus or males. Similarly, a more pronounced anorexia occurred following 12.5, 25, and 50 microg/kg LPS in ovariectomized females that received cyclic estradiol treatment and were tested on the day modeling estrus than in untreated ovariectomized rats. LPS also increased the length of the rats' ovarian cycles, usually by a day, especially when injected during diestrus. As in male rats, when LPS injections were repeated in the same rats, both estradiol-treated and untreated rats failed to display any significant anorexia. The inhibitory effects of LPS on eating in intact and ovariectomized rats were expressed solely as decreases in spontaneous meal frequency, without significant alteration of spontaneous meal size. These data indicate that anorexia following peripheral LPS administration is sexually differentiated and that estradiol is sufficient to produce this response. The mechanism of the pathophysiological effect of estradiol on meal frequency appears to be different from the physiological effect of estradiol on food intake because the latter is expressed solely as a change in meal size.

Acute-Phase Reaction↗

Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A1 and A2A subtype receptor agonists.

1. The cardiovascular effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the adenosine A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate. 2. Intraperitoneal (i.p.) injections of the adenosine A1 receptor agonist CPA led to dose-dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg(-1) CPA were antagonized by i.p. injections of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT), but not by i.p. injections of the adenosine A2A receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8-sulfophenyltheophylline (8-SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardiovascular effects of CPA. 3. The adenosine A2A agonist CGS 21680 given i.p. produced a dose-dependent decrease in blood pressure and an increase in heart rate. These effects of 0.5 mg kg(-1) CGS 21680 were antagonized by i.p. injections of the adenosine A2A receptor antagonist MSX-3, but not by i.p. injections of the antagonists CPT, 8-SPT or caffeine. 4. Central administration (intracerebral ventricular) of CGS 21680 produced an increase in heart rate, but no change in blood pressure. MSX-3 given i.p. antagonized the effects of the central injection of CGS 21680. 5. These results suggest that adenosine A1 receptor agonists produce decreases in blood pressure and heart rate that are mediated by A1 receptors in the periphery, with little or no contribution of central adenosine A1 receptors to those effects. 6. The heart rate increasing effect of adenosine A2A agonists appears to be mediated by adenosine A2A receptors in the central nervous system. The blood pressure decreasing effect of adenosine A2A agonists is most probably mediated in the periphery.

Adenosine↗

Effects of intravitreally and intraperitoneally injected atropine on two types of experimental myopia in chicken.

Atropine, a non-selective muscarinic receptor antagonist, is currently the most potent agent used to prevent myopia in animal models and children. However, the ocular target tissues are not well defined. To learn more about the effect of atropine on experimental myopia, atropine was applied both intravitreally and systemically (intraperitoneally) to chickens wearing either negative lenses or light diffusers. Furthermore, the effect of ipsilateral intravitreal atropine on myopia development in the saline-treated fellow eye was studied. Monocular intravitreal injections of atropine were performed daily for a period of 4 successive days, starting at day 8 post-hatching. Fellow eyes received saline injections. Chicks were fitted with -7D lenses, either over the atropine-injected eyes only (unilateral "lens-induced myopia (LIM)"), or over both eyes (bilateral LIM). Other groups of chicks were fitted with translucent diffusers over the atropine-injected eyes (unilateral "form deprivation myopia (FDM)"). Finally, atropine was intraperitoneally injected for 4 days in chicks that wore monocularly -7D lenses. Refractive errors (RE) were measured with infrared photoretinoscopy and axial length (AL) with A-scan ultrasonography. Atropine prevented development of myopia in both unilateral LIM and FDM in a dose-dependent fashion. Fifty percent inhibition of myopia was observed at a dose of 25 microg (unilateral LIM) or 90 microg atropine (bilateral LIM) and complete inhibition at 750 microg; in unilateral FDM, 50% inhibition occurred at 2.5 microg and almost 100% inhibition at 250 microg. Interestingly, at the highest dose of atropine (2500 microg), the treated eyes became even more hyperopic compared to the saline-injected contralateral eyes with normal visual experience. In the bilateral LIM model, atropine suppressed development of myopia in both the treated and the saline-injected control eye. However, about 8.3 times higher doses were necessary to achieve comparable contralateral suppression. Since this ratio is lower than the vitreous volume to blood volume ratio (about 1:23 in young chicks), it seems unlikely that systemic dilution of the intravitreally injected drug can fully account for the contralateral suppression. Intraperitoneal injection inhibited myopia development only at the highest dose (2500 microg) but, strikingly, this inhibition was still less when the same dose was provided through the vitreous of the fellow eye. Both eyes seem to be coupled by a yet unknown, perhaps neuronal pathway. Estimations of the scleral concentrations of atropine after intravitreal injection are compatible with the assumption that the suppression of myopia by atropine occurs by direct inhibition of scleral chondrocytes.

Animals↗

Intraperitoneal injection of D-galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liver.

In an in vivo 5-week initiation assay model, chemical hepatectomy by hepato-toxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of D-galactosamine (D-gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of D-gal (700 mg kg(-1), i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d-gal (i.p.) the BrdU index was markedly elevated (27.5% +/- 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d-gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using D-gal i.p. is high, so that D-gal i.p. can be considered an effective cell proliferation stimulus.

1,2-Dimethylhydrazine↗

Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans.

Oral administration of lactoferrin (LF), an innate-defense protein present in exocrine secretions such as milk and in neutrophils, is reported to improve host-protection against infections with microorganisms including pathogenic fungi, possibly due to an immunomodulatory effect. This study aimed to evaluate the effect of bovine LF feeding on peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Time course analysis during the 14 days following Candida-priming revealed that LF administration slightly increased the number of peritoneal exudate cells, and significantly enhanced the production of superoxide anion (O2(-)) and nitric oxide (NO) by peritoneal macrophages at day 7. LF administration facilitated NO production and Candida hyphal-growth inhibition by macrophages derived from Candida-primed mice but not non-primed mice, suggesting that the action of LF is dependent on the immune status of the host. LF administration altered the kinetics of cytokines in the peritoneal lavage fluid of Candida-primed mice. Enhancement of cytokine levels by LF was observed for IL-12 at day 5 and IFN-gamma at day 9, but not for TNF-alpha or IL-10. In conclusion, LF feeding augmented the activities of macrophages in a manner dependent on Candida-priming and these effects may be related to enhanced cytokine levels.

Animals↗

Intestinal smooth muscle dysfunction after intraperitoneal injection of zymosan in the rat: are oxygen radicals involved?

Zymosan is frequently used as an activator of granulocytes to study inflammatory responses. We used zymosan as a model to understand the mechanisms involved in intestinal inflammatory diseases, and our special interest was focused on the smooth muscle function. Moreover, we investigated the role of oxidative stress in intestinal pathology after inflammatory processes. Intraperitoneal injection of zymosan induces a peritoneal inflammation, characterised by exudate in the peritoneum and peritoneal fibrosis. Three days after injection of zymosan (25-40 mg/100 g) we measured a decreased beta adrenergic smooth muscle response, while the muscarinic receptor-mediated contraction was not significantly affected. Efforts were made to correlate these observations with the development of oxidative stress; however, the intestinal glutathione balance remained undisturbed and no increase in lipid peroxidation products in the intestine was observed. Our conclusion is the peritoneal inflammation will lead to a release of various mediators, which may destroy receptor systems, among which are beta adrenoceptors. There was no evidence of an important role for reactive oxygen metabolites in this effect.

Animals↗

Intraperitoneal injection of ginseng extract enhances both immunoglobulin and cytokine production in mice.

Ginseng is one of the most widely used Chinese herbal medicines. In this report, the relatively short-term effect of ginseng extract on the immunoglobulin production and cytokine production was studied. The ginseng extract was prepared by boiling the ground ginseng root in 50% ethanol. The specific pathogen-free mice were intraperitoneally (i.p.) injected with various doses of ginseng extract for 3 consecutive days. The results indicated that the serum levels of immunoglobulin (Ig)M, IgG and IgA were significantly elevated after the mice were i.p. injected with 4 g/kg/day of ginseng extract. Under in vitro condition, the lipopolysaccharide (LPS)-stimulated spleen cells showed a dose-dependent increase in secretion of IgM, IgG and IgA. However, at a higher dosage (4 g/kg/day), the amount of IgA secretion began to decline. The serum level of interleukin (IL)-2, interferon (IFN)-gamma[T-helper (Th) 1-type cytokines] and IL-4 and IL-10 (Th2-type cytokines) were significantly elevated after the mice were i.p. injected with 2 g/kg/day or higher doses of ginseng extract. The amount of cytokine secretion by concanavalin A (Con A)-stimulated spleen cells was also significantly enhanced after the mice were i.p. injected with 0.4 g/kg/day or higher dose of ginseng extracted. To further confirm the results from enzyme-linked immunosorbent assay (ELISA), the spleen cells were cultured for 36 hours in the presence of 1 microgram/ml of Con A. Total mRNA was isolated and assayed for mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR). The results revealed that expression of IL-2 and IFN-gamma mRNA were dose-dependently enhanced by the ethanol extract of ginseng. The levels of IL-4 and IL-10 mRNA expression were also elevated in the spleen cells of ginseng-treated mice in comparison with that of the control group. In addition, we observed that the concentrations of IgG1, IgG2a and IgG2b in culture supernatants of spleen cells were dose-dependently increased by in vivo treatment of ginseng extract, suggesting that both Th1- and Th2-type cytokines were involved in IgG production. Our observation in this study demonstrated that the Chinese herbal drug ginseng was able to regulate antibody production by augmenting Th1- (IL-2, IFN-gamma) and Th2-type (IL-4, IL-10) cytokine production.

Animals↗

Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat.

The present study is directed to study: (a) bax translocation and cytochrome c release as mediators of the mitochondrial pathway of apoptosis; (b) Fas-L (Fas-ligand) expression as an indicator of the possible involvement of the Fas/Fas-L signaling pathway; and (c) active caspase-3 expression as the main executioner of caspase-mediated apoptosis, in rats receiving an intraperitoneal injection of the glutamate analogue kainic acid (KA) at a dose of 9 mg/kg, which is sufficient to produce generalized seizures and excitotoxic cell death in the entorhinal cortex. Sub-fractionation studies of entorhinal cortex homogenates have shown cytochrome c and cytochrome oxidase IV localized in the mitochondrial fraction, and Bax localized in the cytosolic fraction. No modifications in the sub-cellular distribution of cytochrome c and Bax have been observed at 6 h and 24 h in KA-treated rats. Morphological studies have shown cytoplasmic shrinkage and nuclear condensation consistent with necrosis in the entorhinal cortex. Many neurons (about 30% of dying cells) are stained with the method of in situ end-labeling of nuclear DNA fragmentation. Yet only about 5% of dying cells have apoptotic morphology. A percentage of dying cells (5% at 6 h and 40% at 24 h) over-express Fas-L but only about 2% of dying cells at 24 h post-injection express cleaved caspase-3 (17 kD). The present data further support the concept that necrosis is the predominant form of cell death in the entorhinal cortex, although caspase-3-dependent apoptotic cell death may play a limited role, in the present paradigm of KA-induced excitotoxicity.

Animals↗

Communication between peritoneal cavity and mediastinal lymph nodes demonstrated by Tc-99m albumin nanocolloid intraperitoneal injection.

Lymphatic drainage from the peritoneal cavity to mediastinal lymph nodes has been reported, indicating that abdominal fluid is not immobile. We studied this movement in rats receiving Tc-99m albumin nanocolloid which has smaller particle sizes than does Tc-99m microaggregated albumin colloid used for liver/spleen imaging. The Tc-99m albumin nanocolloid had a radiochemical purity of 99.33%-99.77% with free pertechnetate of 0.23%-0.67%. During pentobarbital anesthesia, thoracoabdominal images were obtained 4-6 hr after intraperitoneal injection of 350 mCi Tc-99m albumin nanocolloid with 5 ml of normal saline. The images showed symmetrical radiotracer localization in the mediastinal lymph nodes. Scintigraphic demonstration of drainage to the mediastinal region from the peritoneal cavity may be explained by flow directly into mediastinum through the lymphatic system, indicating lymphatic patency between the peritoneal cavity and mediastinum. Absence of visualization may indicate lymphatic block. This type of information concerning lymphatic drainage may have clinical impact for a patient with malignant or intractable ascites. The radionuclide technique is easily performed for this assessment.

Animals↗

Intraperitoneal injection of adenovirus expressing antisense K-ras RNA suppresses peritoneal dissemination of hamster syngeneic pancreatic cancer without systemic toxicity.

We examined the antitumor effect and safety of the adenovirus-mediated expression of antisense K-ras RNA in two peritoneal dissemination models of pancreatic cancer. First, we found that the infection of an adenovirus vector expressing antisense human K-ras RNA (AxCA-AS) induced significant apoptosis in vitro in human pancreatic cancer cells with K-ras mutation. Second, the intraperitoneal (ip) injection of AxCA-AS effectively suppressed the growth of human pancreatic cancer cells in the peritoneal cavity of nude mice. Third, in the hamster syngeneic peritoneal dissemination model, the ip injection of an adenovirus expressing antisense hamster K-ras RNA significantly suppressed the peritoneal growth of hamster pancreatic cancer cells, and no significant systemic toxicity was observed in the treated hamsters. This study suggests a feasibility of the development of a therapeutic strategy against pancreatic cancer based on the adenovirus-mediated transduction of an antisense K-ras construct.

Adenoviridae↗

Intraperitoneal injections of prostaglandin E2 attenuate hyperthermia induced by restraint or interleukin-1 in rats.

1. The purpose of this study was to investigate the effect of the intraperitoneal (I.P.), intravenous (I.V.) or intrapreoptic area (POA) injection of prostaglandin E2 (PGE2) on the body temperature of restrained and unrestrained rats. The effect of I.P. PGE2 on the body temperature of rats during fever induced by I.P. injection of interleukin-1 beta (IL-1 beta) was also investigated. 2. Prior to injection, restrained rats had body temperatures of approximately 1 degree C higher than unrestrained rats. The I.P. injection of PGE2 (0.05 and 0.5 mg kg-1) caused body temperature to fall towards the pre-restraint levels in a dose-dependent manner. This fall in body temperature was preceded by a sharp increase in tail skin temperature that was also dependent on dose. The I.P. injection of PGE2 had no effect on the body temperature of unrestrained animals. 3. The I.V. injection of PGE2 caused very little change in the body temperature of restrained rats. However, when injected I.V. into unrestrained animals, PGE2 caused dose-dependent fevers. The injection of PGE2 (50 ng) into the POA resulted in fever in both restrained and unrestrained animals. 4. The I.P. injection of IL-1 beta (10 micrograms kg-1) caused a biphasic fever that lasted at least 420 min. The I.P. injection of PGE2 180 min after the injection of IL-1 beta caused a transient decrease in the rats' body temperature. This drop in body temperature was not associated with a decrease in metabolic rate. 5. These data support the hypothesis that during restraint stress hyperthermia and IL-1 beta fever, the I.P. injection of PGE2 acts peripherally to lower the body temperature of rats.

Animals↗

Distribution of hematoporphyrin derivative in canine glioma following intraneoplastic and intraperitoneal injection.

Hematoporphyrin derivative (HPD) is a photosensitizing agent that has been used to locate and kill tumors. The distribution of tritiated (3H)-HPD was studied in a transplantable canine glioma model following intraperitoneal or direct intraneoplastic injection. Compared to intraperitoneal administration of 3H-HPD, direct injection resulted in levels that were more than 2.5 times higher in tumor tissue and approximately 10 times lower in skin. Dose-corrected analysis of the data indicated that outside the central nervous system (CNS) the distribution of 3H-HPD is dose-related, regardless of route of injection. Within the CNS, direct injection leads to more efficient uptake of 3H-HPD, especially at the tumor periphery. Fluorescence microscopy confirmed the selective biodistribution of HPD fluorescence within the cytoplasm of tumor cells.

Animals↗

[Analysis of the pharmacokinetics of ethanol injected intraperitoneally and intravenously in rats with different levels of initial alcohol motivation].

Ethanol pharmacokinetics was studied after its intraperitoneal and intravenous administration in rats with different initial level of alcohol motivation using gas chromatography. It was shown that in general pharmacokinetic pattern studied upon both intraperitoneal and intravenous ethanol administration (with respect to resorption and/or distribution), the rate of ethanol elimination including a number of processes leading to a decreased drug content may be an important criterion for the selection of animals with distinct initial levels of alcohol motivation.

Alcohol Drinking↗

Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat.

Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10-40 micrograms/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in tolerance to the response. When soman administration was separated by 2-5 weeks in individual rats, the suppressive effects of the agent again became apparent. Analysis of acetylcholinesterase activity revealed that enzyme inhibition was limited to gastrointestinal areas near the site of injection. There was no significant effect on brain acetylcholinesterase even following IP injection of doses which completely suppressed responding. The IP route may be useful for studying tolerance and other chronic effects of soman without producing generalized toxicity.

Acetylcholinesterase↗

Experience from a long-term carcinogenicity study with intraperitoneal injection of biosoluble synthetic mineral fibers.

The carcinogenic potential in the intraperitoneal cavity of three newly developed biosoluble insulation glass wool fibers (M, P, and V) and one newly developed biosoluble insulation stone wool fiber (O) was investigated and compared to that of a previously developed soluble glass fiber (B). The in vitro dissolution coefficient of the three glass wool fibers ranged from 450 to 1037 ng/cm(2) x h and was 523 ng/cm(2) x h for the stone wool fiber. The in vitro dissolution coefficient of the B fiber was 580 ng/cm(2) x h. Groups of female Wistar rats (strain Crl: Wi BR) were exposed by repeated injections to doses of 0.5, 2, and 5 x 10(9) WHO fibers, which corresponds to between 41 mg to 724 mg fiber injected. In addition, 2 groups of crocidolite were used as positive controls at doses of 0.1 x 10(9) and 1 x 10(9) WHO fibers (0.5 and 5 mg). The in vitro dissolution coefficient of crocidolite is estimated to be approximately 1 ng/cm(2) x h. The protocol of the study and the size distribution of the test samples conformed to the European Commission Protocol EUR 18748 EN, and the study was executed under Good Laboratory Practice conditions. Two of the new insulation wools, fibers M and 0, showed no statistically significant tumorigenic response even at the very high dose of 5 x 10(9) WHO fibers injected. Fibers P and V showed a small tumorigenic response in the ip cavity similar in magnitude to the B fiber, which has been declared in the German fiber regulations as a noncarcinogenic fiber. The response to the soluble insulation fibers was notably different from that of the known carcinogen crocidolite, which produced 53% tumors at a comparatively low dose of 0.1 x 10(9) WHO fibers. The incidence of mesothelioma was found to be highly correlated to the incidence of intra-abdominal nodules and masses at different sites. The incidence of abdominal nodules and masses was highly correlated to the number of animals with ascites. The incidence of chronic peritonitis with fibrotic nodules at different organs also correlated with the incidence of mesotheliomas. Differences in etiology were observed between the massive doses of the highly soluble insulation wools when injected directly into the ip cavity and the lower doses of the extremely insoluble fiber crocidolite. The variability in this reaction and the impairment of animal health put into question the value of these massive doses in evaluating the carcinogenic response of soluble insulation wools. All of the fibers tested fulfilled the exoneration criteria with respect to carcinogenicity according to the European Directive 97/69/EC ("an appropriate intra-peritoneal test has not expressed signs of excessive carcinogenicity"). The dose as defined in the EC-Protocol EUR 18748 EN was 1 x 10(9) WHO fibers with a defined geometric spectrum. The influence of fiber dimensions on the ip tumor response and the difficulty in assessing the influence of the difference in background levels between this and previous studies make direct application of the German TRGS 905 criteria difficult; however, by comparison to fiber B, which in the TRGS 905 is considered as a noncarcinogenic fiber, all of the synthetic mineral fiber types tested in this study also appear to meet the intended German criteria for exoneration.

Abdominal Neoplasms↗

The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.

For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.

Animals↗

[Chromatographic method for quantitative determination of cordycepin in rat brain tissue after intraperitoneal injection of the antibiotic].

A procedure is developed for quantitative estimation of intraperitoneally administered unlabelled cordycepin in acid soluble pool isolated from rat brain tissue. The fraction containing 2'- and 3'-deoxyriboadenosine (cordycepin) in acid soluble pool of rat brain was isolated after consecutive chromatography on columns of Dowex 1 X 8, Dihydroxyboryl-SP 500 and Sephasorb-HP. At the same time, 2'-deoxyriboadenosine was isolated from the acid soluble pool fraction of control animals. Content of the antibiotic in brain tissue was estimated by its difference in these two fractions (control/experiment).

Animals↗