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PubMed1994

Upregulation and induction of surface antigens with special reference to MHC class II expression in microglia in postnatal rat brain following intravenous or intraperitoneal injections of lipopolysaccharide.

The effects of bacterial lipopolysaccharide (LPS) on the expression of surface antigens including major histocompatibility complex (MHC) and complement type 3 (CR3) receptors on microglial cells in the corpus callosum in postnatal rat brain were investigated. When LPS was injected intravenously (i.v.) in 1-d-old rats, the immunostaining of callosal amoeboid microglial cells with OX-18 directed against MHC class I antigen was enhanced 24 h after the injection in comparison with the controls. The expression of MHC class II (Ia) antigen on the same cell type as shown by its immunoreactivity with OX-6 was also elicited especially after 2 intraperitoneal (i.p.) injections of LPS. Thus 7 d after a single i.p. injection of LPS into 1-d-old rats, only a few OX-6 positive cells showing a moderate staining reaction were observed in the corpus callosum. The immunoreactivity diminished 14 d after the injection. However, in rats receiving 2 successive i.p. injections of LPS at 1 and 4 d of age and killed 7 d after the 1st injection, a significant number of intensely stained OX-6 positive amoeboid microglial cells were observed in the corpus callosum. The expression of MHC class II antigens induced by 2 injections of LPS was sustained at least until d 14 when the callosal ramified microglial cells, known to be derived from gradual metamorphic transformation of amoeboid microglia, still exhibited intense immunoreactivity with OX-6. The effect of LPS on the expression of CR3 on amoeboid microglial cells was not obvious after a single injection, but the immunoreactivity with OX-42 was also augmented in rats given 2 i.p. administration of LPS into rats at 1 an 4 d of age. It is concluded from this study that the expression of MHC class I and class II antigens on amoeboid microglial cells in corpus callosum was upregulated and induced respectively after i.v. or i.p. injection of LPS into early postnatal rats. Although relatively fewer in number when compared with OX-18 and OX-42 positive cells, it is suggested that the OX-6 positive cells would have the potentiality to function in antigen presentation in the postnatal rat brain when challenged by the endotoxin.

Animals↗
PubMed2001

Intraperitoneal injection of antisense peptide nucleic acids targeted to the mu receptor decreases response to morphine and receptor protein levels in rat brain.

To determine the effectiveness of peptide nucleic acids (PNAs) in vivo, we designed and synthesized PNAs antisense to the mu receptor, the molecular target of morphine for inducing antinociception. Responsiveness of rats to morphine and the levels of mu receptor expression after treatment was measured. We delivered intraperitoneal injections of antisense PNAs targeted to the mu receptor (AS-MOR), mismatch PNAs (AS-MOR MM), antisense PNAs targeted to the neurotensin receptor subtype 1 (AS-NTR1), or saline and then challenged the rats with 5 mg/kg morphine (intraperitonally) or neurotensin directly into the periaqueductal gray region of the brain. To avoid tolerance, separate groups of animals were tested at 24, 48, and 72 h post-PNA treatment. Only animals treated with the AS-MOR showed a reduction in their antinociceptive response to morphine. The lack of effect of morphine on the AS-MOR rats was profound at 24 and 48 h, but animals tested at 72 h were similar to control groups. At 24 h the AS-MOR rats had a significant 55% decrease in the levels of mu receptor in their periaqueductal gray region, while AS-MOR MM rats showed no significant change. Lastly, the AS-MOR rats continued to show a normal antinociceptive response to neurotensin. This study, therefore, provides additional support for the use of PNAs to target proteins within brain by systemically administered PNAs.

Analgesics, Opioid↗
PubMedDate not supplied

Accumulation in tumor tissue of adoptively transferred T cells: A comparison between intravenous and intraperitoneal injection.

Accumulation of T cells at the tumor is essential in cancer immunotherapy based on adoptive transfer of tumor-specific T cells. To gain further insight into the accumulation process and to evaluate the effect of using different routes of cell transfer, we investigated the accumulation of ovalbumin-specific CD8+ T cells (OT-I) injected either intravenously (IV) or intraperitoneally (IP) into mice carrying a subcutaneous tumor of the ovalbumin-expressing melanoma cell line B16-OVA. Maximal accumulation of the adoptively transferred cells in tumor tissue was observed 5 days after injection, irrespective of the injection route. The route of injection affected neither the total number of adoptively transferred cells found in tumor tissue nor the kinetics of this accumulation. In the spleen, however, the accumulation of adoptively transferred cells was clearly dependent on the injection route. IP injections resulted in a large number of adoptively transferred cells in the spleen on all days analyzed. In comparison, IV injection resulted in significantly fewer adoptively transferred cells in the spleen, and this number decreased over time. The route of injection affected neither the activation status of the adoptively transferred T cells that accumulated at the tumor site, nor the ability of these cells to control tumor growth. Two cell populations, SIINFEKL-tetramer(Low)(Tet(Low))CD69+ CD25+ and Tet(high)CD69- CD25-, were present in tumor samples, whereas only Tet(High)CD69- CD25- cells accumulated in the spleen. In tumors, IV injection resulted in a higher fraction of adoptively transferred cells with an activated phenotype (Tet(Low)CD69+ CD25+) compared with IP injection.

Adoptive Transfer↗
PubMed2003

Effects of intraperitoneally injected selenium and vitamin E in rats anesthetized with halothane.

Halothane, commonly used for anesthetizing humans and animals, is one of the most important volatile anesthetics and may cause the formation of free radicals during its biotransformation. Free radicals may lead to degeneration of liver cells. Vitamin E and glutathione peroxidase (GSH-Px) containing selenium are two natural antioxidants, and these may protect the cellular lipid and lipoproteins against oxidative damage caused by free radicals. Therefore, the purposes of the present study were to investigate the probable protective effects of intraperitoneally administered Se and vitamin E on liver enzymes and to determine some other hematological parameters in the halothane anesthesia of rats. All rats were randomly divided into five groups. The first group was used as a control, and physiological saline (0.9%) was intraperitoneally injected into these animals as a placebo. The second group was used as an anesthesia control group and was only anesthetized with halothane for two hours. The third group received intraperitoneally administered Se (Na2SeO3, 0.3 mg/200 g body weight), the fourth group vitamin E (dl-alpha-tocopheryl acetate, 100 mg/kg body weight), and the fifth group a Se plus vitamin E combination (Na2SeO3, 0.3 mg/200 g body weight + dl-alpha-tocopheryl acetate, 100 mg/kg body weight). The activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, triglycerides, erythrocyte counts, the packet-cell volume, hemoglobin concentrations and neutrophyle rates significantly increased (p < 0.05 to p < 0.01) after halothane anesthesia and returned to near control levels after Se, vitamin E and Se plus vitamin E injections. The values of cholesterol, total protein, white blood cell counts and lymphocyte rates significantly decreased (p < 0.05 to p < 0.01) in the anesthesia control group. However, the levels of albumin, total bilirubin, creatinine, the mean corpuscular volume, the mean corpuscular hemoglobin, and the mean corpuscular hemoglobin concentration were not statistically influenced. In conclusion, we have determined that halothane anesthesia affected some liver enzymes and some other biochemical and hematological parameters. Se, vitamin E and their combination may prevent the increase of liver enzymes after halothane anesthesia. Based upon these results, Se and vitamin E may play an important role in the indication of hepatic cellular injury produced by halothane.

Alanine Transaminase↗
PubMed1990

Antinociception induced by intraperitoneal injection of gentamicin in rats and mice.

Intraperitoneal administration of gentamicin sulfate (5-800 micrograms/kg), but not gentamicin base (23-92 micrograms/kg) produced antinociception in rats and mice, as assessed by the tail-flick, carrageenan-induced articular incapacity tests, and hot-plate tests. The AD50 s in rats (tail-flick test) and mice (hot-plate test) were 11.48 and 147.9 micrograms/kg, respectively, but doses of 200-800 micrograms/kg were required to reduce the hyperalgesia induced in rats by carrageenan. In both species, bell-shaped dose-response curves were obtained, indicating that high doses of gentamicin had little or no effect. Non-effective doses of gentamicin failed to produce a significant increase in morphine antinociception in either rodent species. The possible involvement of N-type voltage-sensitive Ca2+ channels in the mechanism of antinociception induced by gentamicin is considered.

Animals↗
PubMed2002

Carcinogenicity studies after intraperitoneal injection of two types of stone wool fibres in rats.

A summary is given of the pathology results after intraperitoneal (i.p.) injection in rats of insulation wool HT, representing the new biosoluble types. The pathology results are compared with a previously conducted i.p. study with traditional stone wool D6 (with similar chemical composition to MMVF21). The HT fibre is characterized by a relatively high content of aluminium and a relatively low content of silica compared to MMVF21. HT has a high in vitro dissolution rate at pH 4.5, a relatively low dissolution rate at pH 7.5 and is less biopersistent than the MMVF21 fibre. Female Wistar rats received a dose of 2 x 10(9) WHO HT fibres by i.p. injection. The fibres had been size-selected to be largely rat respirable. The negative control group was exposed to saline. Following exposure, the animals were maintained until survival in one group fell below 20%. At this time, all animals were killed. All animals were subjected to a necropsy examination; any gross abnormalities observed at necropsy were subjected to histopathological examination. In addition, histopathology was carried out on a predefined list of tissues. The incidences of lesions and survival in the control and fibre dosed animals were compared using appropriate statistical methods to determine whether the dosed animals showed adverse effects on survival or a positive carcinogenic response. The main protocol for the previously conducted study with D6 (MMVF21) was similar, but the animals were maintained as long as they survived, and the WHO fibre dose was lower. The results of the comparative study showed a marked difference in the i.p. pathogenicity of D6 (MMVF21) and HT in terms of their carcinogenic potential. D6 (MMVF21) caused a statistically significant increase of mesotheliomas in the peritoneal cavity compared to the negative control, but the HT fibre did not cause any mesotheliomas or any increase in other tumour types.

Abdominal Neoplasms↗
PubMed1996

Protective effect of Astragali Radix by intraperitoneal injection against Japanese encephalitis virus infection in mice.

We examined the protective effect of Astragali Radix extracts (AE) by intraperitoneal injection against Japanese encephalitis virus (JEV) infection in mice. A protective effect was observed by all four samples of AE used. However, the degree of effectiveness for each AE was different. The observed survival rates of the groups injected with sample A (from Shanhsi, Japanese name Sansei-syo) and sample D (from Hokkaido) extracts were higher than 80% at 21 d after JEV inoculation. The groups injected with sample B (from Hopei, Japanese name Kahoku-syo) and sample C (from Hsiahsi, Japanese name Sensei-syo) extracts had a 60% survival rate. The increase in hemagglutination inhibition antibody titer was negligible in mice that survived 21 d after JEV inoculation. The antiviral effect of AE was examined by plaque assay in vitro, but no antiviral effect was shown. In mice injected with AE, the peritoneal exudate cell (PEC) numbers increased significantly, compared to the control. In these PEC, active oxygen production was also high. Also the group as a whole displayed a high survival rate against JEV infection, these were so strong. From these results, we propose that the protective effect of AE is dependent on a non-specific mechanism during the early stage of infection, before it shifts to antibody production, and that PEC plays an important role.

Animals↗
PubMedDate not supplied

Human cordonal stem cell intraperitoneal injection can represent a rescue therapy after an acute hepatic damage in immunocompetent rats.

BACKGROUND AND AIM: Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. MATERIALS AND METHODS: Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. RESULTS: Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. CONCLUSIONS: Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.

Animals↗
PubMed1997

Safety studies of the intraperitoneal injection of E1A--liposome complex in mice.

The HER-2/neu (also called c-erbB-2) proto-oncogene is overexpressed in many human cancer cells, including those of breast cancer and ovarian cancer. We have previously shown that adenovirus 5 E1A inhibits HER-2/neu transcription and functions as a tumor suppressor gene in HER-2/neu-overexpressing cancer cells. Liposome-mediated E1A gene transfer suppresses tumor development and prolongs survival of tumor-bearing mice. In support of a phase I clinical trial of an E1A-liposome complex administered to patients with HER-2/neu-overexpressing breast of ovarian cancer, we conducted a series of studies to evaluate the safety of intraperitoneal injection of E1A in normal mice. The cumulative doses used were from five to 40 times the DNA-lipid starting dose proposed for the phase I clinical trial. In this dosing range, the administration of the E1A-liposome complex had no adverse effects on renal, hepatic and hematological parameters studied. No major organ pathologic changes were observed. We concluded that intraperitoneal administration of E1A-liposome complex at the proposed dose would not be expected to produce significant toxicity. The E1A-liposome clinical trial was recently approved by the Recombinant DNA Advisory Committee and Food and Drug Administration for a phase I trial in patients with HER-2/neu-overexpressing breast and ovarian cancer.

Adenoviridae↗
PubMed2006

Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat.

Ghrelin is unique among gut peptides in that its plasma level increases during fasts and its administration stimulates eating. Although ghrelin physiology has been intensively studied, whether its eating-stimulatory effect arises from endocrine-neural signal transduction at peripheral or central sites remains unresolved. To address this issue, we tested the effects of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method available, on ghrelin-induced eating. SDA was verified with a cholecystokinin satiation test, retrograde labeling of vagal motor neurons in the dorsal motor nucleus of the vagus with fluorogold, and anterograde labeling of vagal afferents in the nucleus tractus solitarius with wheat germ agglutinin-horseradish peroxidase. Intraperitoneal injections of 10-40 microg/kg ghrelin stimulated eating as robustly in rats with verified complete SDA as in sham-operated controls. Ghrelin also stimulated eating in rats with total subdiaphragmatic vagotomies. We also recorded the electrophysiological responses of gastric load-sensitive vagal afferent neurons to intravenous ghrelin. Ghrelin (10 nmol) phasically (0-30 s) increased activity in two of seven gastric load-sensitive fibers in the absence of gastric loads and tonically (5-30 min) increased activity in only one fiber. Ghrelin did not affect any of the eight fibers tested in the presence of 1-3 ml gastric loads. We conclude that although phasic increases in plasma ghrelin may affect the activity of a fraction of gastric load-sensitive vagal afferents, the acute eating-stimulatory effect of intraperitoneal ghrelin does not require vagal afferent signaling.

Afferent Pathways↗
PubMed2002

Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice.

NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF but also as a potent angiogenesis inhibitor. This study was designed to assess a therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly intraperitoneal injections of Ad-NK4 could suppress the development of tumor nodules in a nude mouse peritoneal dissemination model. NK4 expression was detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium. Immunohistochemical study of the disseminated tumors showed a remarkable decrease in microvessel density and an increase in number of apoptotic tumor cells in the Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly improved. This study indicates that the intraperitoneal transduction of adenovirus-mediated NK4 gene may be a useful therapeutic modality to prevent the development of peritoneal dissemination of pancreatic cancer.

Adenocarcinoma↗
PubMedDate not supplied

Intraperitoneal injection of dipyridamole increases the life span of tumor bearing mice treated with fluorouracil.

This study was carried out to investigate the effect of the Fluorouracil (5-FU) and Dipyridamole (DP) combination on the growth of P388 murine lymphoid neoplasms. The first stage was to determine the lethal dose (LD 50) for each compound (5-FU, DP) to normal B6D2F1 mice after intraperitoneal (i.p.) injection. The LD 50 were 700 and 54 mg/kg for DP and 5-FU respectively. B6D2F1 mice bearing P388 ascitic tumors and receiving a 4-day schedule of 5-FU (2 mg/kg/day) with DP (100 mg/kg/day) 1 hr before each 5-FU dose were studied. DP was found to lower significantly (p < 0.0001) the mortality of 5-FU in tumor bearing mice by nearly 2.5 fold. This study aims at defining the best dose combination of intraperitoneal injection of 5-FU in conjunction with DP. These data allow a prospective evaluation of 4-day, i.p. 5-FU and DP with an increase of life span without toxic death.

Animals↗
PubMed1994

Upregulation and induction of major histocompatibility complex class I and II antigens on microglial cells in early postnatal rat brain following intraperitoneal injections of recombinant interferon-gamma.

Interferon-gamma when given intraperitoneally by single daily injection into one-day-old rats upregulated the expression of major histocompatibility complex class I antigen on ramified microglial cells in cerebral cortex and induced the expression of major histocompatibility complex class II antigen both on amoeboid and ramified microglial cells present in corpus callosum and cerebral cortex, respectively. In rats receiving single daily injections of interferon-gamma over a period of three consecutive days and killed at the age of seven days, the endothelium exhibited a moderate to weak immunoreaction for major histocompatibility complex class I antigen as detected with the monoclonal antibody OX-18. The immunoreactivity of major histocompatibility complex class I antigen on amoeboid microglial cells was comparable to that of control rats. On the other hand, it was remarkably enhanced on ramified microglial cells and was further intensified with four or six injections of interferon-gamma. In the latter, the endothelial cells also showed a stronger immunoreactivity with OX-18. In rats given three successive injections of interferon-gamma and killed at the age of seven days, 7.5% of amoeboid microglial cells in corpus callosum were induced to exhibit major histocompatibility complex class II antigen as detected with OX-6. An upsurge of the amoeboid microglial cells with major histocompatibility complex class II antigen amounting to about 40% was observed following four and six injections of interferon-gamma. A minimum of four successive injections of interferon-gamma were needed to elicit the expression of major histocompatibility complex class II antigen on ramified microglial cells in cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Incubation periods in six models of intraperitoneally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system.

The pathogenesis of intraperitoneally injected ME7 scrapie has been studied in two Sinc genotypes of mice which gave predictable but widely different incubation periods. Comparisons were made with three other mouse scrapie models and one model in hamsters (involving different strains of agent and an untyped isolate from sheep). Average incubation periods ranged from 114 days in the fastest model (263K/hamsters) to 482 days in the slowest (ME7/Sincp7 mice). There were only small differences between models in the times of onset of replication in spleen and cervical lymph nodes. We suggest that the lymphoreticular stage of pathogenesis initiates neuroinvasion in the peripheral nervous system within a few days to a few weeks of infection. Thereafter, pathogenesis appears to be dominated by neural events and replication in brain becomes detectable after approximately 54% of the remaining incubation period has elapsed, irrespective of its length. It is concluded that the differences between incubation periods of the six scrapie models depend mainly on the rate of a continuous process of replication and spread of infection in the peripheral and central nervous system, which is predetermined by scrapie strain and host genotype. The unpredictability of some other scrapie models (and the natural disease) could be explained by additional factors which restrict neuroinvasion from the lymphoreticular system.

Animals↗
PubMed1994

Tissue distribution of liposomes prepared from synthetic amphiphiles after intraperitoneal injection into mice.

The tissue distribution of 99mTc-labeled vesicles prepared from synthetic amphiphiles containing an amino acid residue (synthetic liposomes) after intraperitoneal (i.p.) injection in Ehrlich solid tumor-bearing mice was investigated. Synthetic liposomes were labeled with 99mTc using stearylamine-diethylenetriaminepentaacetic acid as a chelator. The accumulation of the synthetic liposomes in liver decreased and that in pancreas significantly increased in comparison with those after intravenous injection. Gamma camera images after i.p. injection also indicated high uptake of the synthetic liposomes in pancreas. The radioactivity of the synthetic liposomes in vitro was taken up most highly in pancreas among some excised organs.

Animals↗
PubMed1979

Acute inflammation following intraperitoneal injection of antigen into actively sensitised rats.

Rats actively sensitised to bovine serum albumin (BSA) in Freund's complete adjuvant were challenged by intraperitoneal injection of BSA. By washing out the peritoneal cavities at different times it was possible to divide the changes that occurred into two phases. The first was characterised by the release of histamine and slow reacting substance of anaphylaxis (SRS-A) with an associated extravasation of plasma proteins. The second phase was characterised by an increase in neutrophilic polymorphonuclear cells in the peritoneal cavity. Extracellular enzyme activites were also investigated. The kinetics of these events were studied and are discussed in terms of the possible mechanisms involved.

Animals↗
PubMedDate not supplied

Qualitative X-ray spectrometric study to demonstrate ruthenium in central nervous system structures, after intraperitoneal injection of ruthenium red to adult rats.

A qualitative X-ray spectrometric study oriented to demonstrate ruthenium (Ru) in central nervous system was made after intraperitoneal (i.p.) injection of ruthenium red (RuR) to adult rats. Ru signals were depicted in the brain synaptosomal fraction since 60 min after RuR i.p. administration, corresponding to the latency period of the convulsive model injecting RuR systemically to adult rats. Ru signals were initially detected in pineal gland and periventricular regions, whereas X-rays from Ru atoms in cerebral cortex were detected at longer time intervals after RuR i.p. injection. It is concluded that RuR, a non-liposoluble substance, when injected systemically, passes from the blood stream to brain parenchyma, probably through areas without blood-brain barrier, reaching the neural elements related to the mechanisms of production of convulsions.

Animals↗