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PubMed1989

Comparison of protective immunity and inflammatory responses of pigs following immunization with different Actinobacillus pleuropneumoniae preparations with and without adjuvants.

Three experiments were performed to evaluate the inflammatory response, the antibody response and protection from experimental challenge of various Actinobacillus pleuropneumoniae serotype 5 (Ap5) vaccines in swine. In the first experiment, subcutaneous injections of either a water-in-oil (W/O) emulsion or Freund's complete adjuvant (FCA) caused lesions at the site of injection, while intraperitoneal injection of the W/O emulsion caused no lesions. In the second experiment, intraperitoneal (IP) injection of a W/O emulsion containing unwashed Ap5 cells (6-h culture) and/or supernates from a 24-h culture resulted in severe peritoneal lesions, while W/O emulsion containing PBS-washed Ap5 cells resulted in minimal peritoneal lesions. Ap5 alone or W/O alone failed to cause peritoneal lesions. The third experiment compared the antibody response and protection from challenge of pigs immunized with either 6-h PBS-washed Ap5 cells emulsified in oil - IP, 6-hour Ap5 cells adjuvanted with dimethyl diodacyl ammonium bromide - IP, Ap5 antigen alone - IP, a commercial vaccine - subcutaneously or saline - IP. All groups, except the saline-treated group, responded with high antibody titers to Ap5 2 weeks following vaccination; however, titers from the W/O plus antigen group were significantly higher than the three other groups (P less than 0.05). Following intranasal challenge with Ap5, all animals responded with increased antibody titers. All pigs were euthanized 10 days after challenge and evaluated for pneumonia and the lungs cultured for bacteria. The lungs of all pigs, excepting the W/O plus antigen group, contained pneumonic lesions and A. pleuropneumoniae was cultured from these lesions. These results, along with results from other groups, suggest that intraperitoneal immunization using oil-adjuvanted vaccine may be an effective method for protecting pigs from pneumonia due to A. pleuropneumoniae. Its efficacy may be due to stimulation of local respiratory mucosal immunity.

Actinobacillus↗
PubMed2004

Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 Tesla clinical whole-body system after intraperitoneal contrast injection.

PURPOSE: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) whole-body MR system. MATERIALS AND METHODS: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weigthed images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. RESULTS: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense areas in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. CONCLUSIONS: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats.

Adrenergic alpha-Agonists↗
PubMed1987

Induction of peritoneal fluid eosinophilia and/or monocytosis by intraperitoneal air injection.

We hypothesized that intraperitoneal air might be one of the causes of peritoneal fluid eosinophilia. To test our hypothesis, we injected 100-500 ml of sterile air intraperitoneally into 5 patients receiving continuous ambulatory peritoneal dialysis (CAPD). All patients responded with a transient increase in peritoneal fluid nonerythrocyte cell count (peak counts ranging from 23 to 335 cells/mm3, mean peak count 140 +/- 125) lasting 4 days (after injection of 100 ml of air) to 7 weeks (after injection of 500 ml of air). In 2 patients, the cells were predominantly monocytes (80 +/- 6.5%), whereas in 3 patients, eosinophils predominated (63 +/- 12%), while monocytes (30 +/- 19%) also increased. Resolution of peritoneal fluid pleocytosis correlated temporally with absorption of subdiaphragmatic air. Our results suggest that intraperitoneal introduction of air into CAPD patients can induce peritoneal fluid eosinophilia and/or monocytosis.

Ascitic Fluid↗
PubMed1993

Long-term reversal of diabetes by the injection of immunoprotected islets.

The intraperitoneal injection of insulin-producing islets immunoprotected by an alginate-poly(amino acid) membrane is a potential method of reversing diabetes without the need for lifelong immunosuppression. Previous attempts to demonstrate this technology in large animals have failed, preventing application in humans. We have determined that key factors responsible for these past failures include cytokine (interleukins 1 and 6 and tumor necrosis factor) stimulation by mannuronic acid monomers from alginate capsules with weak mechanical integrity, which results in fibroblast proliferation. With this insight, we formulated mechanically stable microcapsules by using alginate high in guluronic acid content and report prolonged reversal of diabetes in the spontaneous diabetic dog model by the intraperitoneal injection of encapsulated canine islet allografts. Euglycemia, independent of any exogenous insulin requirement, was noted for up to 172 days. Graft survival, evidenced by positive C-peptide release, was noted for as long as 726 days in a recipient receiving a single injection of immunoprotected islets. Histological evidence of viable islets retrieved from the peritoneal cavity 6 months posttransplant confirmed the biocompatibility and immunoprotective nature of this capsule formulation. The finding that intraperitoneal injection of alginate-immunoprotected islets, a minimally invasive surgical procedure, is effective in prolonged (> 1 year) maintenance of glycemic control, without the need for lifelong immunosuppression, may have significant implications for the future therapy of type I diabetes in humans.

Alginates↗
PubMedDate not supplied

Dose-dependent systemic human immunodeficiency virus infection of SCID-hu mice after intraperitoneal virus injection.

SCID mice were engrafted with human foetal liver, thymus and lung. Human cells were subsequently detected among peripheral blood leukocytes for 81% of tested animals and in tissue implants for 100% of tested animals. SCID-hu mice received intraperitoneal injections of human immunodeficiency virus type 1 (HIV1) at from 20 up to 20,000 median tissue culture infectious doses (TCID5). HIV1 infection was detected by means of cell culture and polymerase chain reaction both in blood and implants, up to 58 days after infection. The rate of infection was dependent upon the inoculated dose: the frequency of thymus infection ranged from 14% with 20-500 TCID50 up to 100% with 20,000 TCID50. HIV1 infection was detected less frequently in blood leukocytes than in thymus. Thymus virus load ranged from 40 to 50,000 HIV1 provirus copies per million cells and was not correlated with either infectious dose or viraemia. Thymus T-cell depletion was observed mainly in the CD1+4+8+ immature thymocyte compartment. The same rate of SCID-hu mouse infection was obtained using three different primary HIV1 isolates, suggesting that infection was not restricted to a few particular virus strains. The systemic infection of SCID-hu mice following intraperitoneal virus injection mimics some traits of human HIV infection and provides a promising, novel approach for future investigations in this field.

Animals↗
PubMed1998

Sublethal effects of repeated intraperitoneal cadmium injections on rainbow trout (Oncorhynchus mykiss).

Acute and chronic effects of cadmium have been widely described for different aquatic organisms and exposure routes. However, there is clearly a lack of information on the potential of cadmium to cause genotoxic effects. This work presents genotoxic and nongenotoxic parameters analyzed in cadmium-exposed rainbow trout. The assessment was performed for sublethal levels after long-term exposure using six intraperitoneal injections of 0.5 mg/kg (Day 1), 1 mg/kg (Days 3, 7 and 11), and 2 mg/kg (Days 15 and 19) to allow precise estimation of the dose. Cadmium accumulation in target tissues, essential metal mobilization by cadmium at the subcellular and tissue levels, and induction of metallothioneins were selected as exposure and effect parameters. Induction of micronuclei and variation in DNA content (expressed as variation coefficient in the G1 phase of the cell cycle) in blood cells, determined by flow cytometry, were selected as biomarkers for genotoxic effects. Cadmium accumulation, induction of metallothioneins, and mobilization of essential metals at the subcellular level were observed in different organs in response to cadmium exposure. The highest metallothionein induction was observed in liver, reaching 270+/-90 nmol/g wet tissue in treated fish versus 2.68+/-1.1 nmol/g wet tissue in controls. The highest cadmium accumulation was also observed in the liver (27.8+/-9.5 microgram Cd/g wet wt in treated animals versus 1.0+/-1.7 in the control group). However, no genotoxic effects were observed in blood cells. The frequency of micronuclei was 0.012+/-0.008 for the control group and 0.013+/-0.021 for treated animals. The variation coefficient of G1-phase nuclei was 3.61+/-0.66 and 3.22+/-0.29 for control and cadmium-exposed groups, respectively. Thus, it is concluded that under the experimental conditions employed here, treatment of rainbow trout with cadmium chloride at doses that produce significant toxicological alterations at the tissue and subcellular levels does not provoke observable alterations in the genotoxic parameters considered in this study.

Animals↗
PubMedDate not supplied

Hemopoietic cell kinetics after intraperitoneal single injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widely spread environmental pollutant. Homopoietic system is one of the targets of TCDD in laboratory animals including monkeys. The present study is the hemopoietic cell kinetics in mice, from the severe depression in cellularity of bone marrow and CFU-GM, to their recovery after the intraperitoneal injection of high dosage of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The bone-marrow cellularity and CFU-GM were severely decreased to 37.8% and 48% of the control, respectively until day 1 after exposure to TCDD. They were, however, soon recovered, even overshot the control value. Subsequently, they tended to show decrease and oscillation again to and under the control value. In conclusion, our cell kinetic study has proven the oscillation in bone-marrow cellularity and CFU-GM during the recovery period, of which the observation seems to be useful to extend our understanding in the hematotoxicity of TCDD.

Animals↗
PubMed1993

Effect of diethyldithiocarbamate on diabetogenic action of alloxan in rats.

To determine whether alloxan action is mediated by hydroxyl radicals in vivo, we assayed methane sulfinic acid (MSA), a product of the trapping reaction of dimethyl sulfoxide (DMSO) with hydroxyl radicals. In DMSO-treated rats, the plasma levels of MSA were increased after injection of alloxan (75 mg/kg). This supports the hypothesis that the diabetogenic action of alloxan is mediated by hydroxyl radicals in vivo. The role of cytosolic superoxide dismutase (SOD) in protecting B cells against chemically induced diabetes was studied in rats injected intraperitoneally with diethyldithiocarbamate (DDC). When rats were injected intraperitoneally with DDC (750 mg/kg), the SOD activity at 2.5 h was decreased by 44% in the whole pancreas. The decreased SOD activity was affected by DDC but not by alloxan. Intraperitoneal injection of rats with DDC (750 mg/kg) increased diabetogenic susceptibility to a nondiabetogenic dose of alloxan (20 mg/kg). Subcutaneous injection of vitamin E, prior to administration of both DDC and alloxan, provided partial protection to the rats against the diabetogenic action. These findings suggest that the susceptibility to diabetogenic action of alloxan in B cells is augmented when the cellular SOD activity is inhibited. Thus, cellular SOD may play an important role in the maintenance of B cell function.

Alloxan↗
PubMed1987

Decreased feeding and supraphysiological plasma levels of glucagon after glucagon injection in rats.

The effects of intraperitoneally injected pancreatic glucagon on feeding and on plasma levels of pancreatic glucagon as well as on blood glucose levels and liver glycogen content were investigated in rats, in order to test the physiological relevance of exogenous glucagon's satiety effect. The rats were intraperitoneally injected with various doses of glucagon [60, 240 or 480 micrograms/kg body weight (b.wt.)] or vehicle when they started to eat after a 12 hr period of food deprivation. Only the highest dose of pancreatic glucagon (480 micrograms/kg b.wt.) decreased the size and duration of the first meal after injection. Hepatic vein, hepatic portal vein and aortal plasma pancreatic glucagon levels were increased about 10 fold by 60 and 240 micrograms/kg b.wt. of glucagon and about 30 to 70 fold by 480 micrograms/kg b.wt. of glucagon. All glucagon doses reduced liver glycogen content and increased hepatic vein blood glucose levels similarly. The results indicate that decreased feeding after intraperitoneal injection of glucagon is a pharmacological effect of the hormone, at least under the conditions tested.

Animals↗
PubMed1991

A method for temporary and repeated increase of blood pressure in the rat, using intraperitoneal adrenaline injections.

In experimental studies, permanent hypertension has been considered to be an important factor in aneurysm formation and growth. However, in clinical studies it has been found that saccular aneurysms often develop and rupture in some patients without persistent hypertension. Environmental events that temporarily and repeatedly increase blood pressure do not take an equivalent length of time in vivo but have been noted as factors in the growth or rupture of saccular aneurysms. In order to test the effect of intermittent blood pressure elevations on saccular aneurysm formation and growth, a reliable method for temporarily and repeatedly increasing blood pressure should be developed first and in this paper, such a model is described. It is based on the intraperitoneal injections of adrenaline in rats, a route which does not seem to have been used so far.

Aneurysm↗
PubMed2002

Intraperitoneal protein injection in the axolotl: the amphibian kidney as a novel model to study tubulointerstitial activation.

BACKGROUND: A substantial body of experimental evidence suggests that protein loading causes activation of proximal tubular epithelial cells with consecutive interstitial fibrosis. These studies have mostly been performed using mammalian in vivo models of glomerular damage or tissue cultures of mammalian tubulointerstitial cells. The kidney of the axolotl contains not only closed nephrons, but also nephrons with ciliated peritoneal funnels called nephrostomes that have access to the peritoneal fluid. Injection of protein into the peritoneal cavity fails to expose closed nephrons to a protein load, but causes selective uptake and transient storage of proteins in tubular epithelial cells of nephrons with nephrostomes. The purpose of the present study was to determine whether (a) the axolotl kidney can be used as a model to assess protein uptake by tubular cells in vivo in the absence of glomerular damage, and (b) this is accompanied by any evidence of tubular epithelial cell activation and interstitial fibrosis. METHODS: Male and female axolotl (80 to 120 g of weight) were given a daily intraperitoneal injection of 1.5 mL endotoxin-free calf serum or saline as control. Kidneys were harvested after 4 or 10 days using perfusion fixation for light microscopy (fibrous tissue stain) and saline perfusion for immunohistochemistry (fibronectin, TGF-beta and collagen I). RESULTS: The findings document selective storage of protein and lipids, progressive with time, in proximal tubular epithelial cells of nephrons draining the coelomic cavity. In addition, progressive focal accumulation of fibrous tissue was noted around protein-storing tubules. Immunohistochemical staining demonstrated the presence of fibronectin and TGF-beta in the tubular epithelial cells and interstitial cells. CONCLUSION: The axolotl kidney provides a novel in vivo model to study tubulointerstitial activation and induction of interstitial fibrosis by protein loading. The findings are independent of alterations of glomerular function that may have potential confounding effects on peritubular hemodynamics, pO2, cell traffic, etc.

Ambystoma↗
PubMedDate not supplied

Inhalation administration of all-trans-retinoic acid for treatment of elastase-induced pulmonary emphysema in Fischer 344 rats.

A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus, while inhalation treatment caused greater levels of the drug in lung tissue in comparison to that of injection-treated animals, treatment with ATRA by either route of administration did not cause a reversal of lung tissue damage in this model of elastase-induced emphysema.

Administration, Inhalation↗
PubMed1964

THE SPECIFICITY OF ALLERGIC REACTIONS. VII. IMMUNOLOGIC UNRESPONSIVENSSS, DELAYED HYPERSENSITIVITY, AND CIRCULATING ANTIBODY TO PROTEINS AND HAPTEN-PROTEIN CONJUGATES IN ADULT GUINEA PIGS.

Adult guinea pigs were made unresponsive to a heterologous protein (e.g. bovine gamma globulin, or BGG) or a hapten-protein conjugate (e.g. p-aminobenzoic acid-bovine gamma globulin, or PABAgammamiddot;BGG) by intraperitoneal injection of 80 mg cyclophosphamide and the specific antigen. This immunologic unresponsiveness developed to the specific antigen administered simultaneously with the cyclophosphamide, and not to any variants. Thus, animals unresponsive to PABAgammamiddot;BGG remained unresponsive to the original antigen on challenge with a variant, but formed delayed hypersensitivity and circulating antibody to the variant. The specificity of immunologic unresponsiveness, therefore, seems more closely related to the whole antigen molecule than does delayed hypersensitivity.

Animals↗
PubMed1994

Effects of CCK-8 on ingestive behaviors of suckling and weanling rats.

The present series of experiments was designed to determine the dose-response characteristics of the cholecystokinin suppression effect on rat pups ingesting through suckling and adult modes. Pups at 10-22 days of age were deprived of their dam and food for 6 hr. At test time, the subjects received intraperitoneal injections or intravenous infusions of CCK-8 at 2, 4, 8, or 16 micrograms/kg in saline, or the saline vehicle alone. The pups were permitted to ingest for 30 min immediately after the injection or during the infusion. Ingestion included taking milk from the dam by suckling or feeding from the substrate. Regardless of the route of administration, CCK-8 elicited a low level of suppression across all doses and all ages when pups ingested within the natural suckling situation. In marked contrast, pups ingesting from the substrate in the adult mode suppressed their intake of bovine light cream or chow pellets in a dose-related manner following injections of the peptide. The blockade of the CCK dose-related suppression effect during suckling indicates that a different set of mechanisms governs intake of milk from the mother. The results may be related to the level of arousal required to sustain motivated behaviors while pups engage in the different modes of ingestion.

Animals↗
PubMed2003

Antinociceptive activity of Sempervivum tectorum L. extract in rats.

The extract of Sempervivum tectorum L. (Crassulaceae) containing several flavonoids is widely used as an antiinflammatory agent in folk medicine. Previous studies have demonstrated that various flavonoids or flavonoid-containing plant extracts produce significant antinociception, but no data are available concerning their antinociceptive effect especially at the spinal level. The purpose of the present study was to investigate the antinociceptive activity of Sempervivum tectorum L. extract on acute and inflammatory pain sensitivity in awake rats. The pain sensitivity was assessed by the acute tail- flick test in intact rats and by the paw withdrawal test after carrageenan-induced inflammation using heat stimulus. The plant extract was administered intraperitoneally and intrathecally in rats. The intraperitoneal injection of a high dose of the extract (1000 mg/kg) significantly (p < 0.05) increased the paw withdrawal latency of the inflamed paw. The intrathecal administration (30-300 micro g) caused a small, but significant increase (10%-15%) in tail- flick latency. In the carrageenan-induced inflammatory model, the intrathecally applied extract (30-1000 micro g) significantly decreased, but did not relieve the thermal hyperalgesia. The results suggest that the spinal cord does not seem to play an important role in the antinociceptive effects of this plant extract.

Analgesics↗
PubMed1995

Effect of supplemental folic acid on valproic acid-induced embryotoxicity and tissue zinc levels in vivo.

Valproic acid (VPA) is an anti-convulsant drug known to cause spina bifida in humans. Administration of the vitamin, folic acid, has been shown to decrease the recurrence and possibly also the occurrence of neural tube defects, primarily spina bifida, in humans. Additionally, treatment with a derivative (folinic acid) of folic acid has been reported to decrease the frequency of VPA-induced exencephaly in mice treated with the drug in vivo. A protective effect by folinic acid has not been observed in vitro. The purpose of this investigation was to reexamine the ability of folinic acid to decrease the incidence of VPA-induced neural tube defects in vivo. We also examined the effect of increased intake of folic acid on zinc levels in various maternal and embryonic tissues. Folinic acid, whether administered by intraperitoneal injection or in osmotic mini-pumps, did not decrease the number of mouse fetuses with VPA-induced exencephaly. Dietary supplementation with 10-20 times the daily required intake of folic acid in rodents also failed to decrease the embryotoxicity of VPA. Such dietary supplementation had no effect on zinc levels in maternal liver, brain, or kidney, nor in embryonic tissues. These results indicate that folic acid is not able to reverse the embryotoxicity induced by the anticonvulsant, that there is no apparent effect of high dietary folate intake on maternal or embryonic zinc levels and suggest that folate is probably not involved in the mechanism of VPA-induced embryotoxicity.

Animals↗
PubMed1997

Evidence for a tissue-specific induction of cutaneous CYP2E1 by dexamethasone.

We studied in mouse the effect of topical application of dexamethasone or salicylic acid, on CYP2E1 and CYP3A expression (proteins and/or mRNA) in liver and skin. Dexamethasone was also administered by intraperitoneal injection. Topical application or intraperitoneal injection of dexamethasone increased cutaneous CYP2E1 (8 and 4-fold respectively) whereas the hepatic level of this isoform showed a slight decrease and hepatic CYP3A expression was increased (3-fold). Cutaneous CYP2E1 was increased (3-fold) after topical treatment by salicylic acid. This compound had no effect on hepatic CYP3A and CYP2E1 expression. Cutaneous CYP3A (protein and mRNA) was not detectable in all groups (control or treated animals). Dexamethasone and salicylic acid increased cutaneous CYP2E1 mRNA level (2.5 and 1.4-fold respectively). In conclusion, dexamethasone and salicylic acid induced cutaneous CYP2E1 protein and mRNA level. Cutaneous CYP2E1 induction by dexamethasone is a tissue-specific process.

Administration, Topical↗