Ginseng has been believed to be a powerful tonic by oriental people for a long time and is one of the most popular folk medicine in oriental countries. Intraperitoneal injection of ginseng into rats and mice has been reported to Increase the rates of hepatic RNA and protein synthesis, increase proliforation of rough RES of liver, and enhance alcohol metabolism. We have carried out a study to see the effects of red ginseng powder and extract on in vivo and in vitro metabolism of enflurane and methoxyflurane in male Fisher 344 rats. Red ginseng powder was dissolved in deionized water and dosed for two weeks ad libitum in rats. Hepatic microsomes were prepared and oxidative defluorination of enflurane and methoxyflurane were measured in vitro. Using red ginseng extract, studies were done of both acute and chronic treatment in rats. In chronic experiments, they were dosed with several dosages three times a day for three days; on the fourth day enflurane was administered i.p. and one hour later fluoride levels were mesured in plasma and hepatic microsomes were prepared for in vitro studies as above. In the acute experiment enflurane was administered intraperitoneally eighteen hours after single oral dosage of ginseng and plasma defluorination was measured. There were no statistically significant differences in hepatic microsomal cytochrome P-450 content or defluorination of enflurane and methoxyflurane between control and experimental groups using either red ginseng extract or powder. The results showed that ginseng ingestion did not affect the metabolism of enflurane and methoxyflurane.
Animal ; Enflurane/metabolism* ; Male ; Methoxyflurane/metabolism* ; Panax/metabolism* ; Plants, Medicinal* ; Rats ; Rats, Inbred F344

Intraperitoneal adminstration of radioisotopes is suggested to treat the metastatic ovarian cancer in the pertioneal cavity. Administering beta-emitting radioisotopes into the pertioneal cavity allows the maximum energy delivery to the cancerous cells of the pertioneal wall surface while sparing the normal cells located in deep site of the peritoneal wall. In this study, dose estimates of the peritoneal wall are provided to be used for prescribing the amount of 166Ho-chitosan complex administered. The 166Ho-chitosan complex diffused in the peritoneal fluid may attach to the peritoneal wall surface. The attachment fraction of 166Ho-chitosan complex to the peritoneal wall surface is obtained by simulating the ascites with Fischer rats. Both volume source in the peritoneal fluid and the surface source over the peritoneal wall surface are counted for the contribution to the peritoneal wall dose. The Monte Carlo code EGS4 is used to simulate the energy transfer of the beta particles emitted from 166Ho. A plane geometrical model of semi-infinite volume describes the peritoneal cavity and peritoneal wall. A semi-infinite plane of 10 micrometer in thickness at every 1 mm of depth in the peritoneal wall is taken as the target in dose estimation. Greater han 98 percents of attachment fraction has been observed from the experiments with Fischer rats. Given 1.3 microcurie/cm2 and 2.4 microcurie/ml of uniform activity density, absorbed dose is 123 Gy, 8.59 Gy, 3.00 Gy, 1.03 Gy, and 327 Gy at 0 mm, 1 mm, 2 mm, 3 mm, and 4 mm in depth to the peritoneal wall, respectively.
Ascites ; Ascitic Fluid ; Beta Particles ; Energy Transfer ; Ovarian Neoplasms ; Peritoneal Cavity ; Radioisotopes ; Rats, Inbred F344

OBJECTIVETo investigate the feasibility of strategy of allograft tolerance induction by injection of FasL-decorated donor splenocytes.

METHODSChimeric FasL with core streptavidin (SA-FasL) was efficiently displayed on the surface of splenocytes by the technology of ProtEx™. Heterotopic heart transplant procedures were performed from donor WF rats to recipient ACI rats, F344 rats were used as third-party. Intraperitoneal injection of ACI rats with "decorated" WF splenocytes was used as the approach to induce tolerance in this study. According to different therapeutic strategies, three groups were set up: SA-FasL group (n = 23), SA group (n = 20) and naive splenocytes only group (n = 8). No treatment group was regarded as control (n = 10). Adoptive transfer was underwent with injection of splenocytes from tolerant recipients into naive ACI followed by heart transplant procedures. Mixed lymphocyte reaction (MLR) and third party transplantation were performed to detect allogenic tolerance.

RESULTSThe injection of ACI rats with WF rat splenocytes displaying SA-FasL on their surface resulted in tolerance to donor, but not F344 third-party cardiac allografts. There were 70% cardiac allografts in SA-FasL group achieved long term survival, and it was significantly higher than the rats in other groups (P < 0.05). Adoptive transfer of splenocytes from long-term graft recipients into naive unmanipulated ACI rats resulted in indefinite survival of secondary WF grafts. Donor specific tolerance was identified by MLR and third-party transplant.

CONCLUSIONThe direct display of SA-FasL on the cell membrane in a rapid and efficient manner provides a practical and clinically applicable means of immunomodulation for tolerance induction with considerable therapeutic potential for transplantation.

Animals ; Fas Ligand Protein ; genetics ; immunology ; Heart Transplantation ; immunology ; Male ; Rats ; Rats, Inbred ACI ; Rats, Inbred F344 ; Rats, Inbred WF ; Spleen ; cytology ; metabolism ; Tissue Donors ; Transplantation Tolerance ; immunology

The resistant dextrin NUTRIOSE(R), developed from starch, is expected to act as a prebiotic. The aim of this study was to determine the effects of NUTRIOSE(R) on cecal parameters, short-chain fatty acid (SCFA) concentrations, and fecal excretion in rats. In an initial experiment, twenty-four male Fischer F344 rats were randomly assigned to one of the following four treatments for 14 days: G0 (control diet), G2.5 (control diet + 2.5% of dextrin), G5 (control diet + 5% of dextrin), and G10 (control diet + 10% of dextrin). After 14 days, total cecal weight, cecal content, and cecal wall weight were significantly increased in G5 and G10 compared to G0. At the same time, cecal pH was significantly lower in G10 compared to G0. Total SCFA concentration was significantly higher in G10 than in G5, G2.5, and G0, and significantly higher in G5 than in G0. Acetate, butyrate, and propionate concentrations were significantly increased in G5 and G10 compared to the controls. In a second trial based on a similar design, eighteen male Fischer F344 rats were treated with a control diet supplemented with 5% of dextrin or 5% of fructo-oligosaccharide. The results obtained with NUTRIOSE(R) were similar to those obtained with the fructo-oligosaccharide. In a third experiment, two groups of 5 Fischer F344 rats were orally treated with 100 and 1,000 mg/kg NUTRIOSE(R), respectively, and from 18% to 25% of the dextrin was excreted in the feces. The results of these three studies show that the consumption of NUTRIOSE(R), by its effects on total cecal weight, cecal content, cecal wall weight, pH, and SCFA production, could induce healthy benefits since these effects are reported to be prebiotic effects.
Animals ; Butyrates ; Colon ; Diet ; Diethylpropion ; Feces ; Fermentation ; Humans ; Hydrogen-Ion Concentration ; Male ; Prebiotics ; Rats ; Rats, Inbred F344 ; Starch

OBJECTIVETo investigate the ototoxic effects of streptomycin in vestibular organotypic cultures.

METHODSF344 rats with age at postnatal day three or four were used for this study. The maculae of saccule and utricle were routinely dissected out and cultured with serum-free medium containing various dose of streptomycin for 24 hours. The ciliary turf of vestibular hair cells was stained with fluorescent phalloidin, and its nucleus was stained with to pro-3 DNA probe. The vestibular hair cells were quantitatively counted and photographed under confocal fluorescent microscope.

RESULTSMorphological feature of vestibular hair cells were good in normal control cultures. However, the density of hair cells was decreased in evidence with increase of streptomycin sulfate concentrations. Twenty-four hours after streptomycin cultures, 0.25 mmol/L streptomycin caused a 10% hair cell missing, 50% hair cell loss from 1 mmol/L streptomycin treatment, and more than 75% hair cells gone post-3 mmol/L streptomycin cultures. After streptomycin treatment, the nuclear shrinkage and fragmentation were found in vestibular hair cells, whereas the vestibular supporting cells were normal.

CONCLUSIONStreptomycin induced-vestibular hair cells lesion was in a dose dependent manner with nuclear shrinkage and fragmentation. This may suggest that streptomycin leads vestibular hair cell die through apoptosis.

Animals ; Apoptosis ; drug effects ; Hair Cells, Vestibular ; cytology ; drug effects ; Organ Culture Techniques ; Rats ; Rats, Inbred F344 ; Streptomycin ; adverse effects

BACKGROUNDTreating intramedullary spinal cord gliomas is a big challenge because of limited options, high recurrence rate and poor prognosis. An intramedullary glioma model is prerequisite for testing new treatments. This paper describes the establishment of a rodent intramedullary glioma model and presents functional progression, neuroimaging and histopathological characterization of the tumour model.

METHODSFischer344 rats (n = 24) were randomized into two groups. Group 1 (n = 16) received a 5 µl intramedullary implantation of 9L gliosarcomal (10⁵) cells. Group 2 (n = 8) received a 5 µl intramedullary injection of Dulbecco's modified Eagle medium. The rats were anesthetized, the spinous process of the T₁₀ vertebra and the ligamentum flavum were removed to expose the T₁₀₋₁₁ intervertebral space and an intramedullary injection was conducted into the spinal cord. The rats were evaluated preoperatively and daily postoperatively for neurological deficits using the Basso, Beattie and Bresnahan scale. High resolution magnetic resonance images were acquired preoperatively and weekly postoperatively. When score equal to 0, rats were sacrificed for histopathological examination.

RESULTSRats implanted with 9L gliosarcoma cells had a statistically significant median onset of hind limb paraplegia at (16.0 ± 0.4) days, compared with rats in the control group in which neurological deficits were absent. Imaging and pathological cross sections confirmed intramedullary 9L gliosarcoma invading the spinal cord. Rats in the control group showed no significant functional, radiological or histopathological findings of tumour.

CONCLUSIONSRats implanted with 9L cells regularly develop paraplegia in a reliable and reproducible manner. The progression of neurological deficits, neuroimaging and histopathological characteristics of intramedullary spinal cord gliomas in rats is comparable with the behaviour of infiltrative intramedullary spinal cord gliomas in patients.

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Glioma ; pathology ; Male ; Rats ; Rats, Inbred F344 ; Spinal Cord Neoplasms ; pathology

Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a necrotizing hepatic injury at 4 ~5 months of age, reveals an excess hepatic copper accumulation and is a good model for studying the detail mechanism of cellular copper toxicity. We have observed the effects of copper toxicity on DNA synthesis upon growth stimulation by treating primary-cultured hepatocytes of LEC rat with epidermal growth factor (EGF) and insulin. DNA synthesis measured by [ 3 H]-thymidine incorporation and DNA synthesis S-phase cells in LEC rat significantly decreased when compared to those of normal F344 rat. Since DNA synthesis was impaired in LEC rat, we examined the detail mechanism by determining the histone content, which are involved in DNA stability, and the phosphorylation of nuclear protein. However, the histone contents and phosphorylated nuclear protein upon growth stimulation was intact in LEC rat. These results suggest that a cellular event other than protein phosphorylation required for the initiation of DNA synthesis upon growth stimulation is impaired by copper cytotoxicity in LEC rat.
Animals ; Cinnamomum zeylanicum ; Copper* ; DNA* ; Epidermal Growth Factor ; Hepatocytes ; Histones ; Insulin ; Nuclear Proteins ; Phosphorylation ; Rats* ; Rats, Inbred F344

OBJECTIVEThe present study was designed to investigate the effects of subchronic low level microwave radiation (MWR) on cognitive function, heat shock protein 70 (HSP70) level and DNA damage in brain of Fischer rats.

METHODSExperiments were performed on male Fischer rats exposed to microwave radiation for 90 days at three different frequencies: 900, 1800, and 2450 MHz. Animals were divided into 4 groups: Group I: Sham exposed, Group II: animals exposed to microwave radiation at 900 MHz and specific absorption rate (SAR) 5.953 × 10-4 W/kg, Group III: animals exposed to 1800 MHz at SAR 5.835 × 10-4 W/kg and Group IV: animals exposed to 2450 MHz at SAR 6.672 × 10-4 W/kg. All the animals were tested for cognitive function using elevated plus maze and Morris water maze at the end of the exposure period and subsequently sacrificed to collect brain tissues. HSP70 levels were estimated by ELISA and DNA damage was assessed using alkaline comet assay.

RESULTSMicrowave exposure at 900-2450 MHz with SAR values as mentioned above lead to decline in cognitive function, increase in HSP70 level and DNA damage in brain.

CONCLUSIONThe results of the present study suggest that low level microwave exposure at frequencies 900, 1800, and 2450 MHz may lead to hazardous effects on brain.

Animals ; Cognition ; radiation effects ; DNA Damage ; HSP70 Heat-Shock Proteins ; genetics ; Male ; Microwaves ; adverse effects ; Rats ; Rats, Inbred F344

OBJECTIVETo study modified rat laryngeal transplantation model.

METHODSEighty isogeneic histocompatible F344 rats were randomized into control and experimental groups. Strome model of laryngeal transplantation was established in the the control group, and in the experimental group, the ascending pharyngeal artery was preserved and the base of the tongue, larynx and pharyngolarynx were harvested as a complex allograft followed by end-to-end anastomosis of the both allograft common carotid arteries with the recipient common carotid artery and the anterior jugular vein, respectively. The arterial and nenous patency rate and allograft viability rate were compared between the two groups.

RESULTSThe artery and vein patency rates and graft survival rate were 30%, 15%, and 30% in the control group, and 75%, 65%, and 80% in the experimental group, respectively, showing significant difference between the two groups (P<0.05).

CONCLUSIONIn modified rat laryngeal transplantation model, the allograft viability rate and vessel patency rate are improved, which provides a good model for immunological study of larynx transplantation.

Anastomosis, Surgical ; methods ; Animals ; Laryngectomy ; Larynx ; transplantation ; Models, Animal ; Random Allocation ; Rats ; Rats, Inbred F344 ; Vascular Surgical Procedures ; methods

PURPOSE: Intracranial administration of lipopolysaccharide (LPS) is known to elicit a rapid innate immune response, activate glial cells in the brain, and induce depression-like behavior. However, no study has focused on the changes in glial cells induced by intraperitoneal injection of LPS in vivo.METHODS: Ten adult male Fischer F344 rats underwent [¹¹C]PK11195 PET before and 2 days after intraperitoneal injection of LPS to evaluate the changes in glial cells. The difference in standardized uptake values (SUV) of [¹¹C]PK11195 between before and after injection was determined.RESULTS: There was a cluster of brain regions that showed significant reductions in SUV. This cluster included the bilateral striata and bilateral frontal regions, especially the somatosensory areas.CONCLUSIONS: Changes in activity of glial cells induced by the intraperitoneal injection of LPS were detected in vivo by [¹¹C]PK11195 PET. Intraperitoneal injection of LPS is known to induce depression, and further studies with [¹¹C]PK11195 PET would clarify the relationships between neuroinflammation and depression.
Adult ; Animals ; Brain ; Depression ; Electrons ; Humans ; Immunity, Innate ; Injections, Intraperitoneal ; Lipopolysaccharides ; Male ; Neuroglia ; Positron-Emission Tomography ; Rats ; Rats, Inbred F344