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At least 1,261 records · Page 70Linked to original sources
PubMed1992

Retinoic acid enhances monoclonal antibody WE3 reactivity in the regenerate epithelium of the adult newt.

Monoclonal antibody (mAb) WE3 recognizes an antigen that is developmentally expressed in the wound epithelium during adult newt limb regeneration. Experiments were designed to determine whether retinoic acid (RA), dissolved in dimethyl sulfoxide (DMSO) and administered by intraperitoneal injection, would enhance the temporal appearance of the WE3 antigen. RA given on days 1 or 4 after amputation, when the WE3 antigen is not yet detectable, resulted in moderate reactivity to mAb 2 days after injection and strong reactivity throughout the wound epithelium 4 days after injection. DMSO alone had no enhancing effect. RA also caused limb skin epidermis to exhibit reactivity to mAb WE3, initially near the amputation level, but then also more proximally. By 4 and 6 days after RA injection, epidermis of the flank, eye lid, and unamputated hind limbs also became strongly reactive to mAb WE3. Outer layers of skin epidermis were shed, resulting in an epidermis only one or two cells thick. Epidermis of newts given DMSO alone remained non-reactive to mAb WE3. When RA was given on days 7 and 10 after amputation, when a low level of mAb WE3 reactivity is already present in the wound epithelium, a considerable enhancement of mAb WE3 reactivity occurred through the next few days. No such enhancement was seen with DMSO alone. RA also greatly increased mAb WE3 reactivity in the wound epithelium of denervated limbs, in which case the wound epithelial reactivity to mAb WE3 is normally low. Retinol palmitate also increased mAb WE3 reactivity. The results raise the possibility that the WE3 antigen is a component of most if not all retinoid target tissues in newts.

Animals↗
PubMed2002

Constitutive expression of heterologous N-methyl-D-aspartate receptor subunits in rat adrenal medulla.

An RT-PCR analysis revealed constitutive expression of mRNA for N-methyl-D-aspartate (NMDA) receptor (NR)-1, NR-2C, and NR-2D subunits in rat adrenal and pituitary glands, in addition to brain and retina. Constitutive expression of mRNA was detected for the NR-2A subunit in pituitary but not adrenal gland. Although on Western blotting assays adrenal medulla exhibited expression of NR-1 subunit protein without expression of NR-2C and NR-2D subunit proteins, an immunohistochemical investigation clearly showed selective localization of proteins for NR-1, NR-2C, and NR-2D subunits in adrenal medulla but not in adrenal cortex. Prior treatment with different glycosidases invariably resulted in a marked increase in immunoreactivity to the anti-NR-1 antibody in both hippocampus and adrenal medulla. An intraperitoneal injection of a blocker of NMDA receptor channel, but not NMDA itself, led to marked potentiation of DNA binding activity of the transcription factor activator protein-1 in adrenal nuclear extracts 2 hr after administration. These results suggest that heteromeric NMDA receptor channels may be constitutively and functionally expressed with glycosylation of NR-1 subunit under the influence of tonic stimulation by circulating agonists such as L-glutamate in rat adrenal medulla.

Adrenal Medulla↗
PubMed1981

Effect of taurine on seizures induced by 4-aminopyridine.

The effect of intraperitoneally injected taurine against the convulsive activity induced by 4-aminopyridine (4-AP) was studied in 12- to 15-day-old mice. At a dose of 2.6 mg/kg, taurine increased the latency of clonic seizures from 7 to 20 minutes, reduced the incidence of tonic seizures from 92% to 30% and the postconvulsive mortality from 80% to 31%. The injection of EDTA prior to the administration of taurine prevented the protective effects of the amino acid. GABA and glycine at the same doses did not protect against 4-AP-induced seizures. 4-AP caused a small increase (19%) in 45Ca accumulation by mice brain synaptosomes incubated in a Krebs-HEPES medium containing low CaCl2 (0.1 mM) and also slightly potentiated the veratrine and potassium-induced increase in calcium accumulation. 4-AP at concentrations of 1-2 mM caused a marked increase (100%-500%) of 45 Ca accumulation by synaptosomes incubated in a Krebs-bicarbonate medium containing 2.5 mM CaCl2. This increase was completely antagonized by taurine but not by GABA of glycine. The present observations suggest that the anticonvulsant effect of taurine might be mediated by 4-AP-calcium-taurine interactions.

4-Aminopyridine↗
PubMed1983

Learning deficits on avoidance task and hippocampal lesions in area CA3 following intraperitoneal administration of 3-acetylpyridine.

Young adult mice of the ddN-F26 strain were given a single intraperitoneal injection of 3-acetylpyridine (3-AP) at a dosage of 200 mg/kg body weight. Two weeks after this treatment, learning on avoidance task was tested with a training apparatus called a jump-box. Each mouse was subjected to 30 trials of training per week for 3 or 4 weeks. Contrasted to untreated mice, the mean performance of the 3-AP-treated mice on avoidance training was significantly reduced in every weekly training session. However, since the learning scores of individual 3-AP-treated mice were highly varied, these mice were divided into several groups according to the characteristics of their learning patterns in order to analyze the relationships between learning ability and brain damage. It was found that there was a close association between the rate of learning deficits and the degree of destruction of the pyramidal cells in area CA3 of the hippocampus in mice treated with 3-AP. The present data suggest that the area CA3 neurons play an important role on the acquisition of avoidance task and memory formation.

Animals↗
PubMed1987

Nonresident macrophages in peripheral nerve of rat: effect of silica on migration, myelin phagocytosis, and apolipoprotein E expression during Wallerian degeneration.

The selective toxicity of silica quartz dust to macrophages was used to assess the role of these cells in Wallerian degeneration and nerve repair. Left sciatic nerves of adult Wistar rats were crushed and one group of animals received repetitive intraperitoneal injections of silica (200 mg two times per week starting 1 day prior to injury), whereas the control group received saline. Unexpectedly, silica treatment did not impair the initial invasion of (hematogenous) macrophages into the degenerating distal nerve stump as revealed by histological and immunocytochemical methods. However, 4 weeks after the lesion three specific events in Wallerian degeneration were significantly inhibited in silica-treated animals: 1) inhibition of phagocytosis and degradation of myelin, 2) delay in disappearance of nonresident macrophages from regenerating nerve, 3) reduction of synthesis and/or secretion of apolipoprotein E in resting macrophages. On the other hand, axonal regrowth and remyelination were not affected by silica. These in situ experiments support and extend previous studies suggesting specific functions for nonresident macrophages in Wallerian degeneration of peripheral nerve.

Animals↗
PubMed1987

Effect of acute ethanol administration on brain levels of tetrahydropapaveroline in L-dopa-treated rats.

The effect of ethanol on the concentration of the aberrant dopamine metabolite, tetrahydropapaveroline (THP), in brains of L-dopa-treated rats has been evaluated. THP was isolated from rat brain extract by a newly developed multiple stage separation technique that is highly specific for the alkaloid. THP, dopa, and dopamine were assayed by high-performance liquid chromatography with electrochemical detection. THP was not found in brains of untreated animals. However, levels of 0.42 pmol THP per g brain were observed in animals that received L-dopa (200 mg/kg) by intraperitoneal injection (IP) 90 min before decapitation. Administration of ethanol (3g/kg) IP to L-dopa-treated animals at time intervals ranging from 60 to 240 min before decapitation resulted in significant increases in brain levels of THP as compared to L-dopa-treated animals. Maximum levels of THP (4.02 to 4.82 pmol/g brain) were observed when ethanol was given at time intervals ranging from 80 to 180 min before the animals were killed. Administration of ethanol and L-dopa, as compared to the administration of L-dopa only, markedly increased brain levels of dopa and dopamine. Maximum brain levels of THP, dopa, and dopamine in animals administered ethanol plus L-dopa as compared with L-dopa-treated animals represented a 1048%, 325%, and 84% increase, respectively. These results strongly support the concept that the concentration of THP in the brain of intact animals can be enhanced by ethanol administration.

Animals↗
PubMed1991

The stability of proton T2 effects of oxygen-17 water in experimental cerebral ischemia.

The gerbil model of unilateral cerebral ischemia has been used to test the temporal and spatial stability of the MRI T2 effects of oxygen-17 water. Following unilateral carotid ligation, symptomatic animals were given a single large intraperitoneal injection of H2(17)O and the distribution and stability of the brain T2 effects were followed with a spin-echo sequence. In contrast to the ischemic areas, the perfused tissue shows a marked and prolonged loss in intensity with little evidence of diffusion of the T2 effect of 17O into the ischemic tissue.

Animals↗
PubMed1992

T1 snapshot FLASH measurement of rat brain glioma: kinetics of the tumor-enhancing contrast agent manganese (III) tetraphenylporphine sulfonate.

The ultrafast inversion recovery snapshot FLASH technique was used to determine the kinetics of the contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS) in experimental brain tumors in rats. In the first part of the investigation this technique was validated with the conventional inversion recovery spin-echo method by comparing in vivo T1 data of a normal rat brain. Agreement between T1 values obtained from both techniques was complete, as tested for a large number of pixels in identical coronal slices. In the second part the fast IR snapshot FLASH method was applied to study the effect of the NMR contrast agent MnTPPS on the T1 relaxation time of experimental gliomas in rat brains. T1 of normal brain tissue (1024-1035 ms), tumor (1217 ms), and edema (1199 ms) was determined with the inversion recovery version of the snapshot FLASH imaging technique. After intraperitoneal injection of MnTPPS (0.25 mmol/kg body wt) T1 decreased exponentially to 56% of control in tumor and to 62% in muscle. In normal and edematous brain tissue no significant changes in T1 were observed up to 5 h after injection of the contrast agent. Once the T1 contrast between tumor and peritumoral brain tissue had reached a saturation, the enhancement persisted for several hours to days. Therefore application of this contrast agent resulted in a sharp demarcation between glioma and peri-tumoral edema.

Animals↗
PubMedDate not supplied

Acute effects of phenytoin on peripheral nerve function in the rat.

The acute effect of intraperitoneal injection of phenytoin on rat peripheral nerve was studied. Conduction velocities in the ventral caudal nerve were measured hourly and phenytoin blood levels were obtained 4 to 5 hours after injection. Conduction velocity decreased by 23% in the 25 phenytoin-treated animals from a control value of 30.0 plus or minus 1.3m/sec (mean plus or minus SEM) to a 4-hour value of 23.0 plus or minus 1.3 m/sec (P less than 0.001). The phenytoin blood level 4 hours after injection was 45.0 plus or minus 1.3 micrograms/ml. Amplitudes of evoked muscle action potentials in the treated group decreased by 37% from control values. High levels of phenytoin induce prompt slowing of nerve conduction velocity within hours, which may be mediated by mechanisms similar to those responsible for toxic central effects.

Action Potentials↗
PubMed2005

Protective effects of lycopene and tomato extract against doxorubicin-induced cardiotoxicity.

The protective effect of tomato extract and lycopene on acute doxorubicin (DOX) myocardial toxicity was evaluated in mice. DOX toxicity, induced by a single intraperitoneal injection (15 mg/kg), was revealed by an elevated serum CPK(MB) and histopathological observations. Tomato extract (1.2 and 2.4 g/kg, i.p.) and lycopene (1.7 and 3.5 mg/kg, i.p.) prevented the rise in serum CPK(MB) and ameliorated cardiac cell injury. These results suggest that tomato extract and lycopene inhibit DOX cardiotoxicity and might serve as a novel combination chemotherapeutic agent with DOX to limit free radical-mediated organ injury.

Animals↗
PubMed1991

Dose response study of N-nitrosodiethanolamine initiation of rat hepatocarcinogenesis.

Initiating activity of N-nitrosodiethanolamine (NDELA) for rat liver carcinogenesis was investigated using an 8-weeks bioassay system. Male F344 rats were initially treated with a single intraperitoneal injection of NDELA at one of five dose levels: 1,600, 800, 400, 200, or 100 mg/kg. Two weeks later, the rats were placed on 0.02% 2-acetylaminofluorene (2-AAF) or 0.05% phenobarbital (PB) containing diet for 6 weeks. All animals were subjected to 2/3 partial hepatectomy 4 weeks after the NDELA treatment, and killed at the end of the eighth week. NDELA itself exerted low toxicity in terms of body weight gain. Clear dose-dependent initiating activity of NDELA was observed in terms of development of glutathione S-transferase placental form (GST-P) positive liver cell foci, this being more apparent with PB promotion than with 2-AAF where the enhancing regimen itself caused multiple lesion development. Initiating potential of NDELA, however, was much lower than that observed for diethylnitrosamine in our previous work.

2-Acetylaminofluorene↗
PubMed1992

Transplacental genotoxicity of triethylenemelamine, benzene, and vinblastine in mice.

Transplacental cytogenetic effects of triethylenemelamine (TEM), benzene, and vinblastine on maternal mice and their fetuses have been investigated using micronucleus and sister chromatid exchange (SCE) as genetic endpoints. CD-1 mice were treated on day 14 and 15 of gestation with TEM (0.125, 0.25, and 0.5 mg/kg), benzene (439,878, and 1,318 mg/kg), and vinblastine (0.5, 1, and 2 mg/kg) by intraperitoneal injection at 24 hr intervals, and sacrificed 40 hr after the first injection. Erythrocytic precursor cells in maternal bone marrow and fetal livers (2-4) from each pregnant mouse were used for the micronucleus and/or the SCE analyses. Significant dose-related increases in both micronuclei and SCE were found in maternal bone marrow and fetal liver following TEM treatment. Benzene at the highest dose (1,318 mg/kg) also caused a significant increase in micronuclei and SCE in both maternal bone marrow and fetal liver cells. The embryonic genotoxic effect of TEM was much higher than that of benzene for both genetic endpoints, and the frequency of micronuclei induced by benzene was higher in fetal liver than in maternal bone marrow cells. Vinblastine, a spindle poison, induced micronuclei but not SCE. Micronuclei induction by vinblastine was 7 fold greater in maternal bone marrow than in fetal liver cells. All three chemicals were cytotoxic in maternal bone marrow cells, but not in fetal liver cells except for TEM, which showed a weak cytotoxicity in fetal liver cells in the micronucleus assay. These results indicate that TEM, benzene, and vinblastine are transplacental genotoxicants in mice.

Animals↗
PubMed1989

Early postimplantation embryolethality in mice following in utero inhibition of adenosine deaminase with 2'-deoxycoformycin.

Adenosine deaminase (ADA) catalyzes the hydrolytic deamination of adenosine (or 2'-deoxyadenosine) to inosine (or 2'-deoxyinosine). Previously, we have shown that ADA activity is subject to strong cell-specific developmental regulation in placental tissues of mice between days 6 and 11 of gestation (Knudsen et al.:Biology of Reproduction 39:937-951, 1988). In the present study, we examined the effects of intrauterine exposure to 2'-deoxycoformycin (dCF; pentostatin), a potent irreversible inhibitor of ADA, on early postimplantation development. Deoxycoformycin was administered to pregnant ICR mice as a single intraperitoneal injection at a dose of 5 mg/kg on one of days 6 through 11 of gestation (plug day 0). A marked increase in the incidence of implantation site resorptions was observed following treatment specifically on days 7 (61% resorbed) or 8 (78% resorbed). No effect was observed following treatment on days 6, 9, 10, or 11. ADA-immunoreactive protein was shown, by ABC-immunoperoxidase staining on days 7 or 8 of gestation, to be present at high levels in decidual cells of the antimesometrial region but at below-detectable levels in the embryo. Treatment of pregnant dams with dCF on day 7 produced a complete (greater than 99%) inhibition of ADA activity in the antimesometrial decidua by 30 min, induced excessive cell death in the prospective neural plate and primary mesenchyme of the trilaminar disc by 6 h, and arrested embryonic development at an early somite stage. These results suggest that the antimesometrial decidua plays a protective role in preventing an inappropriate accumulation of endogenous ADA substrates in the implantation site.

Adenosine Deaminase↗
PubMed2001

Preliminary evidence of toxicity associated with the benthic cyanobacterium Phormidium in South Australia.

In April 2000, the water supply for Yorke Peninsula in South Australia was deemed non-potable when extracts from a proliferation of the benthic cyanobacterium Phormidium aff. formosum in Upper Paskeville Reservoir were found to be lethally toxic by intraperitoneal injection into mice (400 mg kg-1). Routine water quality monitoring had failed to detect the development of the Phormidium until complaints of musty taste and odour, attributable to the production of 2-methyl-isoborneol (MIB), were received from the consumers. The 185 ML open-balancing storage, receiving filtered and chloraminated water from the River Murray, was isolated from the drinking water supply and a health alert was issued to approximately 15,000 consumers. The identity of the toxin(s) is thus far unknown, but clinical symptoms of toxicity in mice and chemical characteristics are distinct from the known major cyanotoxins. Preliminary characterisation of this toxin indicates that it has low solubility in water and organic solvents and is strongly associated with the particulate cellular material of the filaments. Toxicity of extracts was diminished by boiling and by treatment with chlorine, but not by chloramines. Further testing of floating cyanobacterial mats in the Torrens Lake in the city of Adelaide (Phormidium aff. formosum) and Myponga Reservoir (Phormidium aff. amoenum) in 2000/2001 was also found to be toxic by mouse bioassay. Toxicity is yet to be confirmed in monospecific cultured strains and further studies are required to identify the toxin and assess its health significance. Genetic characterisation of isolates has commenced in an attempt to classify their relatedness and to assist in the rapid identification of potentially toxic strains.

Animals↗
PubMed2002

MFO induction potential of fish species native to the Swan-Canning Estuary, Western Australia.

The use of mixed function oxygenase (MFO) enzymes as a potential biomarker of pollution in the Swan-Canning Estuary was investigated in four indigenous fish species, Perth herring (Nematalosa vlaminghi), sea mullet (Mugil cephalus), yellowtail trumpeter (Amniataba caudavittata), and black bream (Acanthopagrus butcheri). Each experimental fish was intraperitoneally injected with 10 micrograms/kg of 3,3',4,4',5-pentachlorobiphenyl per kilogram of fish using corn oil as a carrier. Controls were injected with 1 mL corn oil per kilo. Induction of the hepatic ethoxyresorufin-O-deethylase (EROD) activity was measured 10 days post injection. Perth herring did not survive the experimental period due to the poor ability of this fish to endure captivity and handling. Yellowtail trumpeter demonstrated a low EROD induction response (2-fold relative to controls), while sea mullet displayed a moderate EROD induction potential (3.5-fold relative to controls). Because of their lower EROD induction potential, yellowtail trumpeter and sea mullet were not considered the most suitable bioindicator species for Western Australian estuarine waters. Black bream has desirable population traits and had a relatively high MFO induction potential response (9-fold relative to controls). From the results it was concluded that, when using EROD induction as a biomarker, black bream is a suitable fish to use as a bioindicator species for investigations into the health of the Swan-Canning Estuary.

Animals↗
PubMed1995

The spin-trap N-tert-alpha-phenyl-butylnitrone prolongs the life span of the senescence accelerated mouse.

Free radicals and oxidative damage have been proposed as underlying factors in aging, in chronic and degenerative diseases of aging and in acute clinical conditions. To test involvement of free-radicals in such processes, spin trapping agents which quench more reactive radicals to produce long-lived stable radical adducts have been used as an experimental strategy. Spin traps protect against oxidatively induced injury in numerous in vitro and in vivo model systems involving different organs. A model system for mammalian aging is afforded by the senescence accelerated mouse (SAM-P8), which exhibits many features characteristic of mammalian aging but with a much shortened lifespan. Daily intraperitoneal injection of the spin trap N-tert-alpha-phenyl-butylnitrone (PBN) was administered to male or female mice after they reached maturity at 3 months of age. PBN treated animals as compared with control sham injected animals revealed a remarkable extension of the mean life span in both male and female populations. Overall, a 50% mean survival rate was found of 42 weeks for control as compared to 56 weeks for the PBN administered groups. These results show that the spin trap PBN can prolong lifespan and support the free radical theory of aging.

Aging↗
PubMed1999

Regulation of macrophage inflammatory protein-1 alpha expression and function by endogenous interleukin-10 in a model of acute inflammation.

In this study we have determined the role of endogenous interleukin (IL)-10 on leucocyte recruitment and production of the CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) in a murine model of acute inflammation. Intraperitoneal injection of zymosan produced a dose-dependent cellular infiltration which was concomitant with MIP-1alpha release in the lavage fluids. Release of this chemokine had a functional role since treatment of mice with a specific anti-MIP-1alpha antibody reduced both neutrophil and monocyte accumulation into the peritoneal cavity. An unexpected increase in cell influx and MIP-1alpha production was measured following depletion of resident peritoneal macrophages, as achieved by a 3-day liposome treatment. A similar result was obtained when the zymosan peritonitis response was elicited in IL-10 knock-out mice. In summary we propose a functional cross talk between endogenous IL-10 and this CC chemokine during the host inflammatory response.

Acute Disease↗
PubMed2000

Inhibition of intracellular cathepsin activities and suppression of immune responses mediated by helper T lymphocyte type-2 by peroral or intraperitoneal administration of vitamin B6.

We reported that pyridoxal phosphate (PAP), a coenzyme form of vitamin B6, strongly inhibits activities of cathepsin B and weakly inhibits those of cathepsins S, K, and C in vitro. Either intraperitoneal injection or peroral administration of medication doses of vitamin B6 in the diet caused dose-dependent inhibition of hepatic cathepsins B, L, S, and C, and the inhibition was exhibited much more significantly in the case of a high protein diet than in a low protein diet. Administration of vitamin B6 induced the suppression of immune responses against ovalbumin (OVA) mediated by helper T lymphocyte type-2, based on the suppression of antigen processing by cathepsin B inhibition, as in the case of CA-074 administration, a cathepsin B specific inhibitor. Ovalbumin-dependent production of immunoglobulins IgE, IgG1 and interleukin IL-4 was suppressed by administration of medication doses of pyridoxal (PA) or pyridoxine (PI), while the production of IgG2alpha and interferon (INF)-gamma mediated by helper T lymphocyte type 1 was not changed. Administration of medication doses of vitamin B6 caused the inhibition of intracellular cathepsin B activity due to suppression of the functions of helper T lymphocyte type-2.

Administration, Oral↗