Showing papers on "Intraperitoneal injection published in 1984"

Protective Activities of the Filamentous Hemagglutinin and the Lymphocytosis-Promoting Factor of Bordetella pertussis in Mice

Abstract: Protective activities of the filamentous hemagglutinin (FHA) and the lymphocytosis-promoting factor (LPF) of Bordetella pertussis were compared by active and passive protection tests with intracerebral or respiratory challenge in mice. Mice immunized twice by intraperitoneal injection of 8 micrograms of FHA or glutaraldehyde-inactivated LPF were protected after aerosol challenge. One intraperitoneal injection of inactivated LPF also protected mice from intracerebral challenge; the dose protecting 50% of the mice was 8.5 micrograms. However, one intraperitoneal injection of 48 micrograms of FHA or two weekly intraperitoneal injections of 20 micrograms did not protect mice from death after intracerebral challenge. Injection of affinity-purified antibody to LPF from mouse hybridomas or from goats gave a dose-dependent protection against aerosol challenge. The smallest dose giving protection was 80-90 micrograms. Polyclonal or monoclonal antibody to FHA at doses of 1,440 micrograms or 360 micrograms, respectively, gave very little protection from disease after respiratory challenge. These data indicate that active immunization of mice followed by respiratory challenge with B. pertussis is a useful model to identify protective antigens.

Sustained viremia in experimental hamster scrapie. Brief report.

Abstract: After an intraperitoneal injection of scrapie agent into hamsters, a viremic phase is maintained from day 10 to at least day 40 post infection. Infectivity can be detected in the brain as early as 5–10 days after inoculation.

In vivo metabolic effects of hyperglycemia in murine radiation-induced fibrosarcoma: a 31P NMR investigation.

Abstract: The hyperglycemia-induced in vivo metabolic changes produced in subcutaneous murine RIF-1 tumors, grown on female C3H/Anf mice, were examined with 31P surface-coil NMR. Serum glucose levels were elevated 4-fold by bolus intraperitoneal injection of 0.3 ml of an aqueous 50% glucose solution. Tumor pH was calculated from the chemical shift of Pi and relative phosphocreatine and ATP concentrations were determined by Simpson's rule integration of the peak areas. Tumor pH decreased by ca. 0.45 unit over 2 hr while phosphocreatine concentrations decreased by ca. 50% over the same time period (n = 9). Initial tumor pH correlated inversely with the initial peak intensity ratio of Pi:ATP (r = -0.77). In a significant number of tumors (n = 4), two pH populations were observed. In these tumors, one population was unaffected by hyperglycemia and the other showed a decrease in pH. In the other tumors (n = 5), the pH distribution broadened as the pH decreased. In these tumors, the observed decreased in phosphocreatine concentration correlated with that calculated from the effect of measured tumor pH on the intracellular creatine kinase equilibrium (n = 18, r = 0.91). This correlation and consideration of the Pi distribution in the tumor suggest that the pH measured by 31P NMR is weighted heavily by intracellular pH for the RIF-1 tumor. The presence of two distinct tumor pH populations or a broadened pH distribution likely reflects variations in tumor microcellular environment. Control experiments showed negligible changes in tumor pH and high energy phosphate concentrations after bolus intraperitoneal injection of 0.3 ml of isotonic saline. In addition, negligible changes in leg muscle pH and high energy phosphate concentrations were observed after glucose injection into mice with or without tumors. These results indicate that hyperglycemia induced by intraperitoneal glucose injection is effective in lowering the tumor pH of the murine RIF-1 tumor.

Spinal opiates affect sexual behaviour in rats

Abstract: Enkephalin-containing cells in the substantia gelatinosa of the spinal cord1 participate in the neural processing of painful stimuli2,3. Spinal opiates may also be involved in the perception of sensory stimuli related to reproduction, as probing of the uterine cervix stimulates sexual behaviour in rats4 and also induces an analgesia5 which is partially dependent on opiate receptor mechanisms in the spinal cord6–8. We now report that the intrathecal injection of morphine into female ovariectomized rats pretreated with oestradiol benzoate and progesterone inhibits sexual receptivity while injection of the opiate receptor antagonist naloxone enhances it. Similarly, intrathecal injection of morphine increases while injection of naloxone decreases the number of intromissions before ejaculation in male rat. Intraperitoneal injection of morphine or naloxone has no behavioural effect. Recent studies have suggested that brain opiates are involved in the control of sexual behaviour9–11. The results reported here indicate that sexual behaviour may also be influenced by spinal opiates.

A comparison of isometallothionein synthesis in rat liver after partial hepatectomy and parenteral zinc injection.

Abstract: The time course of hepatic zinc-isometallothionein synthesis was studied in the regenerating liver and compared with that produced after the parenteral injection of zinc (6 mg of Zn2+/kg). In the regenerating liver, zinc levels rose rapidly after partial hepatectomy and reached a maximum at approx. 14h before declining to approximately normal levels at 48h post-operation. During this 48h period most of the zinc was incorporated into metallothionein. Purification of the latter into the charge-separable isometallothioneins (i.e. MT1 and MT2) showed that, in the regenerating liver, there was an unequal distribution of zinc between the two isoproteins. Thus at operation the endogenous thionein had an MT2/MT1 ratio of 1; after regeneration this ratio increased, and all times during the time course there was more MT2 than MT1. In contrast, the intraperitoneal injection of zinc produced a biphasic uptake of zinc into the liver with maxima at 10h and 32h. During the first phase of zinc uptake, metallothionein synthesis increased rapidly and, unlike the regenerating liver, the MT2/MT1 ratio of 1 remained constant. Thereafter, this ratio increased in a manner analogous to that exhibited by the regenerating liver. Half-life determinations for thionein disappearance/degradation shows that MT2 and MT1 were degraded with half-lives (t1/2) of 26.18h and 16.44h respectively in the regenerating liver and 14.75h and 9.3h after zinc injection. Thus thionein disappearance/degradation in the regenerating liver was slower than that seen after zinc injection. However, in both situations MT2 was always removed at a slower rate than MT1. Calculation of the rates of thionein synthesis (assuming the above disappearance rates were constant throughout the time course) showed that, in the regenerating liver, the rate of MT2 synthesis was approximately twice that of MT1. This was not the case after zinc injection, where both isometallothioneins were synthesized in equal amounts. These results demonstrate that the rates of synthesis of MT2 and MT1 can be altered according to the metabolic status of the cell and suggest a specific role for MT2 during liver regeneration.

Lymphocytosis-promoting factor of Bordetella pertussis alters mononuclear phagocyte circulation and response to inflammation.

Abstract: Previous results from our laboratory demonstrated that purified lymphocytosis-promoting factor (LPF), a protein toxin from Bordetella pertussis, inhibited the migration of murine macrophages in vitro. The current study examined the in vivo effects of LPF on mononuclear phagocyte circulation and response to an inflammatory stimulus. Intravenous injection of mice with 200 ng of LPF produced a prolonged monocytosis which peaked with a fivefold increase on day 5 after injection. LPF (200 ng) also inhibited by more than 75% the increase in peritoneal inflammatory macrophages induced by intraperitoneal injection of thioglycolate broth, phytohemagglutinin, or paraffin oil. The inhibition was significant when thioglycolate was given 1 h or 2 or 4 days after LPF but not when thioglycolate was given 2 or 4 days before LPF. The LPF-induced monocytosis on day 5 after injections was not altered by the intraperitoneal injection of thioglycolate broth. The leukocytosis-promoting and macrophage-inhibiting properties of LPF were the same in N:NIH(S) and C3H/HeJ mice. Treatments of LPF that reduced the leukocytosis-promoting effect of LPF also reduced the ability of LPF to inhibit the macrophage response. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the thioglycolate-induced increase in peritoneal macrophages. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of mononuclear phagocytes at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both effects of LPF and is consistent with the in vitro inhibition of macrophage migration by LPF.

Treatment of experimental erosive arthritis in rats by injection of the muralytic enzyme mutanolysin.

Abstract: A single intravenous injection into rats of 0.4 mg of the muralytic enzyme mutanolysin, given as long as 3 d after an arthropathic dose of peptidoglycan-polysaccharide polymers derived from group A streptococci (PG-APS), resulted in a complete resolution of acute arthritis and the prevention of chronic joint disease. When administration of mutanolysin was delayed until 14 d after the injection of PG-APS, a great reduction in the severity of chronic inflammation was still observed. Quantitation of the amount of PG-APS present in the limbs, spleen, and liver by a solid phase enzyme-linked immunoassay indicated that the tissues of mutanolysin-treated rats contained as much PG-APS as tissues of PBS-treated control rats. In addition, rats treated with mutanolysin immediately after receiving an intraperitoneal injection of PG-APS developed a transient limb edema similar to that seen in rats after the injection of PG-APS digested to a small fragment size in vitro with mutanolysin. We hypothesize that mutanolysin acts in vivo by degrading PG-APS to small fragments that persist but are no longer arthropathic.

Effects of Dichloroacetate on Pyruvate Metabolism in Rat Brain in Vivo

Abstract: Summary was lowered. However, the effect of DCA on the lactate level in the cerebrospinal fluid'in the patients has not been reported. The effects of dichloroacetate On the activity of the Therefore, we investigated the in vivo effects of small and large pyruvate deh~drogenase (PDH) and associated changes doses of DCA on the activity of the PDH complex in the brain in the lactate and glucose levels in rat brain were investigated in and consequent changes in the lactate and glucose levels in rats. vivo. The average activities of the active form of the PDH complex in the brain, liver and muscle of starved rats were respectively 0.40 f 0.04, 0.07 f 0.04, and 0.17 + 0.11 pmol/ min/g tissue, and amounted to 21, 11, and 16% of the total activity of the complex. Intraperitoneal injection of DCA (125 mg/kg) increased the percentage of the active form of the PDH complex in the brain, liver, and muscle to 107, 40, and 84%, respectively. DCA significantly lowered the lactate and glucose concentrations of the brain and blood. A lower dose of DCA (1 2.5 mg/kg) also caused significant increase in activity of the PDH complex in the brain, but did not significantly change the lactate or glucose concentration of the brain. These results suggest that DCA crosses the blood-brain barrier reasonably well.

Acute target organ toxicity of 1-nitronaphthalene in the rat.

Abstract: 1-Nitronaphthalene (1-NN) produced respiratory distress and centrilobular liver necrosis in male Sprague-Dawley rats after a single intraperitoneal injection (100 mg kg-1). Microscopic examination of the lungs of rats killed 24 h after the injection revealed a highly selective non-ciliated bronchiolar (Clara) cell necrosis as the only remarkable lesion. Pretreatment of animals with phenobarbital offered complete protection from the respiratory distress induced by 1-NN, but increased the severity of the hepatotoxicity. Pretreatment with SKF-525A protected against 1-NN-induced liver necrosis, but did not alter the incidence or severity of the respiratory distress. Under similar conditions, this pattern of toxicity was not seen with the structural analogue 2-nitronaphthalene.

Effects of lead and hyperthermia on prenatal brain growth of guinea pigs

Abstract: The effects of lead at blood levels of 100 μg/100ml or less on the brains of young animals have not been clearly defined, and little is known of its effects and interactions with other agents on prenatal brain development. This study examined the effects of subclinical doses of lead acetate given to pregnant guinea pigs on the development of the embryo brain. At 9 A.M. on day 20 or 21 of pregnancy, guinea pigs were given 6, 12.5, or 25 mg/kg body weight of 0.5% lead acetate in distilled water by intraperitoneal injection. Some of the animals at each dose rate were also exposed to hyperthermia at 11 A.M. on the day of injection and the following day. Another group was exposed to hyperthermia without lead treatment. A saline-treated control group was used for comparison. Mean levels of lead in blood 1 hour after dosing ranged between 65 and 128 μg/100 ml and at 24 and 72 hours between 65 and 96 μg/100 ml. Brain weights of newborn guinea pigs in the 12.5- and 25-mg lead acetate group were significantly reduced compared with control values. Body weights of all groups receiving lead were not significantly differently different from those of controls. There was no indication of interaction between hyperthermia and lead acetate in doses of 6 or 12.5 mg/kg. At 25 mg/kg plus hyperthermia, there appeared to be a strong synergistic response, with an incidence of 88% micrencephaly compared with 5% in the group given 25 mg/kg without hyperthermia and 46% in the hyperthermia without lead group. The results indicate that subclinical levels of lead can retard prenatal brain growth, and this effect is potentiated by hyperthermia.

Oligomycin toxicity in intact rats

Abstract: Intraperitoneal injection of oligomycin into the rat (0.5 mg per kg, corresponding to the LD33 dose) reduces the oxygen consumption by about 50%, whereas the arterial pO2 remains normal. The large extent of this decrease points to an involvement of liver and muscle tissue. Triiodothyronine pretreatment (3 doses of 0.075 mg/100 g body weight) is not able to prevent this effect. From the blood metabolites measured glucose, pyruvate and the parameters of lipid metabolism remain unchanged; only lactate is significantly increased, causing compensated metabolic acidosis. Heart rate, systolic blood pressure and electrocardiogram are essentially unchanged. Oliguria, reduced renal excretion of urea and increase of plasma urea also indicate a nephrotoxic action. The results are discussed in comparison with some effects of experimental uremia.

Macrophages in resistance to rickettsial infections: protection against lethal Rickettsia tsutsugamushi infections by treatment of mice with macrophage-activating agents.

Abstract: Peritoneal macrophages of BALB/c and C3H/HeN mice activated in vivo by intraperitoneal inoculation of viable Mycobacterium bovis strain BCG or the nonliving macrophage-activating agent Propionibacterium acnes (Corynebacterium parvum), were resistant to infection with Rickettsia tsutsugamushi, and they killed bacteria that did gain entry into the intracellular environment of these cells. This macrophage resistance to infection and intracellular destruction of rickettsiae was dependent upon development of an immune response to the activating agents, since macrophages elicited by sterile inflammatory agents failed to display either microbicidal activity unless cells were exposed to factors present in lymphokine-rich culture fluids from antigen or mitogen stimulated spleen cells (LK) in vitro. C3H/HeN mice that had been treated with activating agents, but not sterile inflammatory irritants, also survived intraperitoneal inoculation of up to 10(4) R. tsutsugamushi. This nonspecific protection required the chronic presence of activated macrophages: acute immune response induced by intraperitoneal injection of PPD into mice inoculated intradermally with BCG, or intraperitoneal inoculation of conconavalin A, were not sufficient to induce survival of rickettsial disease, although macrophages from these animals were activated to kill rickettsiae at the time of challenge. The critical nature of activated macrophages in nonspecific protection against rickettsial infection was demonstrated with the macrophage-defective C3H/HeJ mice. These mice are equally as susceptible as C3H/HeN mice to intraperitoneal inoculation of R. tsutsugamushi, but do not develop activated macrophages in response to BCG infection, and are not protected against lethal rickettsial challenge following BCG treatment.

The tissue-specific accumulation of hepatic zinc metallothionein following parenteral iron loading.

Abstract: The synthesis in various tissues of the unique metal-binding protein, metallothionein, can be influenced by the administration of certain trace elements. Zinc and cadmium, both of which bind to metallothionein, are most widely recognized as potent inducers. Preliminary results in our laboratory suggested that iron loading causes a marked accumulation of hepatic zinc metallothionein. In this report the effects of parenteral iron administration on metallothionein concentration in various tissues are presented. Male chicks (300-350 g) received (ip) either a single injection (+1 Fe) of iron (10 mg Fe/kg, as FeCl/sub 3/), two injections (+2 Fe) given 24-hr apart, three injections (+3 Fe) each given 24-hr apart, or an equivalent volume of 0.9% saline (control). Twenty-four hours following the final injection, chicks were killed and tissues analyzed for cytoplasmic zinc and metallothionein (Zn-MT). The parenteral administration of ferric iron, FeCl/sub 3/, resulted in a marked tissue-specific accumulation of zinc as metallothionein. In chicks given +2 Fe, hepatic Zn-MT increased more than 10-fold with a third injection (+3 Fe) causing no further change. The concentration of Zn-MT in renal and pancreatic tissue was unaffected by iron loading. An increase in hepatic Zn-MT was evident prior to detectable changes in total hepatic iron.more » The administration of other ferrous iron compounds at a similar rate produced comparable changes in hepatic Zn-MT. Feeding excess dietary iron, however, had no effect on liver Zn-MT levels even though similar hepatic iron concentrations were attained. Results indicated that parenteral administration, but not feeding, of various iron compounds causes a marked increase in zinc metallothionein, specifically in liver tissue.« less

Mononuclear phagocyte function in head and neck cancer: depression of murine macrophage accumulation by low molecular weight factors derived from head and neck carcinomas.

Abstract: In earlier experiments chemotactic responsiveness of peripheral blood monocytes obtained from patients with head and neck cancers was found to be markedly depressed. In an attempt to attribute this defect in migration to an influence excited by low molecular weight factors of less than 25,000 daltons, derived from the tumor, Amicon filtrates of head and neck cancer cells were administered sub-cutaneously to C3H mice 24 hrs. before the intraperitoneal injection of concanavelin A. Subsequent macrophage accumulation into the peritoneal cavity was quantified. A clear inhibition of macrophage infiltration was found, particularly when filtrates of poorly differentiated tumors were used. Injection of filtrates from healthy oral mucosa were negative, whereas mouse mammary carcinoma filtrates strongly inhibited accumulation.

In Vivo Activation of Macrophages but not Natural Killer Cells by Picolinic Acid (Pla)

Abstract: Intraperitoneal injection of PLA into C57BL/6 mice induced high levels of macrophage-mediated cytostatic activity. Maximal cytostatic activity was found 3 days after injection of 100 mg/kg of PLA. In contrast, natural killer cell activity was not affected by PLA. Thus, PLA selectively modulates macrophage activity without influencing NK activity.

Immunomodulation and antitumor effects of MVE-2 in mice.

Abstract: The biological response modifier maleic anhydride-divinyl ether (MVE-2) can activate natural killer (NK) cells and macrophages and can act as an immunoadjuvant for T and B cells. MVE-2 activates macrophages following intravenous or intraperitoneal injection in a compartmentalized manner, i.e., peritoneal macrophages (i.p. injection) or alveolar macrophages (i.v. injection). It activates NK cells in vivo but not in vitro, a dichotomy that may be secondary to interferon production. Splenic NK cell activity is not prolonged by the multiple injection of MVE-2; instead, it induces a state of NK cell hyporesponsiveness, which may limit its therapeutic efficiency. Therapeutic properties of MVE-2 are largely limited to nonspecific immunoprophylaxis, which may be associated with NK cell activation but which does not necessarily correlate with the level of splenic NK cell activation. Minimal therapeutic efficiency consisting of a slight prolongation in survival is observed in mice with preexistent disease treated with MVE-2. Prolonged survival is observed only in those animals placed on therapy soon after tumor cell challenge (experimental metastasis) and not in mice with established spontaneous metastasis. The need to manipulate the animal model (MVE-2 injection prior to or rapidly following tumor challenge) seems to predict that this agent is unlikely to be clinically useful against preexistent metastatic tumor burden, although some efficiency may be associated with local treatment into the pleural or peritoneal cavity.

Distribution, metabolism and excretion of N-nitrosobis(2-hydroxypropyl)amine in Wistar rats.

Abstract: The metabolic fate of the carcinogen N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Wistar rats was studied. The blood level of (1-/sup 14/C)BHP after a single intraperitoneal injection, administered at a carcinogenic dose of 3 g/kg body weight, reached a maximum within 1 h. Whereas a relatively high concentration of /sup 14/C was found in the blood and target organs, such as the lung, liver, thyroid gland and kidney 1 h after the treatment, most of the radioactive labelling had disappeared from the tissues by 24 h after injection. Most of the administered /sup 14/C was eliminated via the urine; 90.8% was excreted in the urine within the 24 h period, 5.5% in the feces and 3.2% by way of expired air. Studies in rats with exteriorized bile flow demonstrated that about 11% of the intraperitoneally administered /sup 14/C was excreted via the bile in 24 h. Analysis by h.p.l.c. detected BHP (78.1% of the dose), HPOP (1.5%), glucuronides of BHP (4.3%) and HPOP (0.16%), MHP (0.03%) and unknown metabolites (6.0%) in the urine 24 h after the treatment. Besides these metabolites, BOP and two unidentified metabolites were also detected in the blood, lung, liver or kidney of rats 3 h after themore » treatment. These results suggest the involvement of BHP metabolites, HPOP, MHP and BOP, in carcinogenesis and in particular lung carcinogenesis induced by BHP in rats.« less

Effects of acrylamide and other sulfhydryl compounds in vivo and in vitro on staining of motor nerve terminals by the zinc iodide‐osmium technique

Abstract: The zinc iodide-osmium technique blackens motor nerve terminals by selectively staining synaptic vesicles. Intraperitoneal injections of acrylamide (30 mg/kg/day, 5 times each week) cause inhibition of staining by this technique so that approximately one third of the end-plates in rat sternocostalis muscle are unstained after 24 hours, and by 17 days more than 70% are unstained. This is not associated with nerve fiber degeneration. A similar inhibition of staining can also be shown after prior incubation of the sternocostalis muscle in 4 mM acrylamide in oxygenated Ringer's solution. Intraperitoneal injection of the thiol group blocker N-ethylmaleimide also causes marked inhibition of staining of motor end-plates by this method. Dithiothreitol, which prevents the oxidation of thiol groups, will partly prevent the inhibition of staining by both acrylamide and N-ethylmaleimide, when given in vivo.

Growth-inhibitory effect of prostaglandin D2 on mouse glioma cells

Abstract: The effects of prostaglandin D2 (PGD2) on the growth of mouse malignant glioma cells were studied in vitro and in vivo. The in vitro studies consisted of various concentrations of prostaglandins (PG's) being added to cultures of mouse glioma cells. At concentrations above 2.5 micrograms/ml, PGD2 strongly inhibited the proliferation of glioma cells, whereas PGE2 had no effect at the same value. Exposure to 5.0 micrograms/ml PGD2 for more than 2 hours resulted in inhibition of glioma cell proliferation. This growth-inhibitory effect of PGD2 was related to the inhibition of DNA synthesis of the cells. The in vivo studies were performed with a subcutaneously transplanted mouse glioma model. Injection of 0.5 mg/kg PGD2 into the tumor was more effective than the same concentration given by intraperitoneal injection. In mice with intracranially transplanted glioma, daily intraperitoneal injection of 0.5 mg/kg PGD2 had no significant effect on survival time.