Showing papers on "Intraperitoneal injection published in 2000"
TL;DR: HIF‐1 activation could contribute to protective brain preconditioning, which could be used in high‐risk deliveries and other clinical situations.
Abstract: Hypoxia-inducible factor-1 (HIF-1) is a heterodimer composed of HIF-1alpha and HIF-1beta protein subunits. This transcription factor is essential for the activation of hypoxia-inducible genes like erythropoietin, some glucose transporters, the glycolytic enzymes, and vascular endothelial growth factor. Because HIF-1 activation may promote cell survival in hypoxic tissues, we studied the effect of hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic preconditioning (8% O2 for 3 hours), a treatment known to protect the newborn rat brain against hypoxic-ischemic injury, markedly increased HIF-1alpha and HIF-1beta expression. To support the role of HIF-1 in protective preconditioning, we also studied the effect of two other known HIF-1 inducers, cobalt chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and neuroprotection in newborn brain. HIF-1alpha and HIF-1beta protein levels were markedly increased after intraperitoneal injection of CoCl2 (60 mg/kg) and moderately increased after intraperitoneal injection of DFX (200 mg/kg) 1 to 3 hours after the injections. Preconditioning with CoCl2 or DFX 24 hours before hypoxia-ischemia afforded 75 and 56% brain protection, respectively, compared with that in vehicle-injected littermate controls. Thus, HIF-1 activation could contribute to protective brain preconditioning, which could be used in high-risk deliveries and other clinical situations.
427 citations
TL;DR: Differences in brain penetration of antidepressant drugs depending on the presence of the mdr1a gene may offer an explanation for differences in the treatment response at a given plasma concentration.
215 citations
TL;DR: It was found that both melatonin and 5-methoxytryptamine were approximately equipotent in enhancing the activities of superoxide dismutase and glutathione reductase in the kidney and liver, while 5-MethOxytryptophol displayed a weaker effect.
Abstract: Male Sprague-Dawley rats were randomly divided into four groups. Two of the groups received a single intraperitoneal injection of melatonin and 5-methoxytryptamine (5 mg/kg body weight), respective...
121 citations
TL;DR: Melatonin exerts a therapeutic effect on CCl4‐induced acute liver injury in rats, possibly through its antioxidant action, judging from the levels of serum transaminases, indices of liver cell damage.
Abstract: The therapeutic effect of melatonin on acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). Melatonin (10, 50, or 100 mg/kg body weight [BW]) was intraperitoneally administered to male Wistar rats 6 hr after intraperitoneal injection of CCl4 (1.6 g/kg BW) at which time an apparent liver injury occurred. This post-melatonin administration dose dependently prevented the progression of liver injury at 24 hr after CCl4 injection, judging from the levels of serum transaminases, indices of liver cell damage. Rats injected with CCl4 alone showed an increase in liver lipid peroxide (LPO) content and a decrease in liver reduced glutathione content at 6 and 24 hr after the injection. The post-melatonin administration dose dependently ameliorated both changes found at 24 hr after CCl4 injection. Rats injected with CCl4 alone showed an increase in liver triglyceride (TG) content and decreases in serum TG concentration and liver tryptophan 2,3-dioxygenase (TDO) activity, a marker of the inhibition of liver protein synthesis by CCl4, at 6 and 24 hr after the injection, and also a decrease in serum albumin concentration at 24 hr. The changes in serum TG, albumin concentration, liver TG content, and TDO activity found at 24 hr after CCl4 injection were not ameliorated by the post-administration of melatonin. The same administration of melatonin dose dependently reduced liver LPO content in CCl4-untreated rats. These results indicate that melatonin exerts a therapeutic effect on CCl4-induced acute liver injury in rats, possibly through its antioxidant action.
115 citations
TL;DR: In this paper, the relative efficacy of various routes of immunisation with pIHNVw-G was evaluated using 1.8 g rainbow trout fry vaccinated via intramuscular injection, scarification of the skin, intraperitoneal injection, intrabuccal administration, cutaneous particle bombardment using a gene gun, or immersion in water containing DNA vaccine-coated beads.
110 citations
TL;DR: It is indicated that feeding HF diets diminishes the enterogastric inhibition of gastric emptying by intestinal oleate and diminish the ability of CCK to inhibit gastrics emptying.
Abstract: Rats maintained on low-fat (LF) or high-fat (HF) diets were fitted with gastric cannulas and duodenal catheters. Intraperitoneal injection of 0.250–2.0 μg/kg cholecystokinin (CCK) significantly inh...
108 citations
TL;DR: A dissociation between the two brain mediated events, one of which is dependent on the integrity of the vagus nerve (social exploration) while the other (fever) is apparently generated by different mechanisms which may include circulating pyrogens.
Abstract: Vagal afferent signals, have been implicated in cytokine mediated interactions between the periphery and the central nervous system. Studies in experimental animals have shown that cytokine induced activation of brain mediated responses to infection such as fever, sickness behaviour and pituitary-adrenal activation, are inhibited by subdiaphragmatic vagotomy. We have previously proposed that the peripheral signal to the brain in fever is of a humoral nature while others have suggested that either neural afferents or a mixture of both humoral and neural signals may be involved. The objective of the present study was to examine further the role of vagal transmission, in mediating the febrile response to a systemic injection of IL-1beta in rats and to compare this with changes in social exploration behaviour. Intraperitoneal injection of IL-1beta (1.0-30.0 microg/kg) inhibited social exploration in rats and this was attenuated in vagotomized animals. Injection of increasing concentrations of IL-1beta (0.1-1.0 microg/rat) induced significant (P<0.001) increases in core body temperature. However, in contrast to effects on social exploration, the increase in temperature was not inhibited by vagotomy at any of the doses used. These observations demonstrate a dissociation between the two brain mediated events, one of which is dependent on the integrity of the vagus nerve (social exploration) while the other (fever) is apparently generated by different mechanisms which may include circulating pyrogens.
104 citations
TL;DR: In conclusion, vagotomy itself has no marked effect on circulating endotoxin levels or the production of IL-1beta, IL-6, or corticosterone in blood after an intraperitoneal injection of LPS.
Abstract: The vagus nerve appears to play a role in communicating cytokine signals to the central nervous system, but the exact extent of its involvement in cytokine-to-brain communication remains controversial. Recently, subdiaphragmatic vagotomy was shown to increase bacterial translocation across the gut barrier and thus may cause endotoxin tolerance. The current experiment tested whether or not vagotomized animals have similar systemic responses to endotoxin challenge as do sham-operated animals. Subdiaphragmatically vagotomized and sham-operated animals were injected intraperitoneally with one of three doses (10, 50, 100 μg/kg) of lipopolysaccharide (LPS) or vehicle, and blood samples were taken at 15, 30, 60, 90, and 120 min after the injection. The intraperitoneal injection of LPS increased circulating LPS levels at all time points examined. In addition, all three doses of LPS significantly increased serum interleukin (IL)-1β, IL-6, and corticosterone in both control and vagotomized rats. In conclusion, vagotomy itself has no marked effect on circulating endotoxin levels or the production of IL-1β, IL-6, or corticosterone in blood after an intraperitoneal injection of LPS.
103 citations
TL;DR: The fact that treatment with TNF bp accelerated and improved the rats' ability to develop a febrile response supports the view that the fever is beneficial, since all other metabolic responses measured in this study were normalized more effectively in those rats that developed a faster and more pronounced increase in body temperature.
Abstract: Injection of a high dose of lipopolysaccharide (LPS) induces a septic-shock-like state, which can be accompanied by phases of hypothermia and phases of fever. In the present study we monitored body core temperature and locomotor activity, both by remote radiotelemetry, as well as changes in food intake, body mass and water intake for 3 days after an intraperitoneal (i.p.) injection of a high dose of LPS (5 mg/kg) along with sterile 0.9% saline or a neutralizing form of the soluble tumor necrosis factor (TNF) type 1 receptor (referred to as TNF-binding protein, TNF bp). Intraperitoneal injection of LPS rapidly induced high concentrations of TNF in the plasma and peritoneal lavage fluid. TNF was undetectable in the plasma and peritoneal lavage fluid of animals co-injected with LPS and TNF bp, implying neutralization of peripheral bioactive TNF. Administration of LPS induced hypothermia by about 1.5°C, which lasted for 5 h after injection. During the light-time periods of days 2 and 3 after injection, the rats developed a robust fever. Treatment with TNF bp resulted in a faster recovery from the LPS-induced hypothermia so that the rats developed a pronounced fever on the day of injection. Locomotor activity during night-time periods was suppressed in LPS-treated animals. The LPS-induced depression of night-time activity was not antagonized by co-injection of TNF bp. On day 1 after the injection of LPS, food intake reduced to virtually zero, water intake fell to about 30% of the control value and body mass dropped by 25 g (about 10% of total body mass). With the exception of body mass, these variables recovered slowly during days 2 and 3 after LPS injection, but did not reach the control values. The LPS-induced decreases in food intake, body mass and water intake were significantly attenuated by the treatment with TNF bp. These results confirm that TNF contributes significantly to the rats' responses to intraperitoneal injection of a high dose of LPS. The fact that treatment with TNF bp accelerated and improved the rats' ability to develop a febrile response supports the view that the fever is beneficial, since all other metabolic responses measured in this study were normalized more effectively in those rats that developed a faster and more pronounced increase in body temperature.
93 citations
TL;DR: Tempol-H is a systemic in vivo radioprotector of C3H mice and is associated with less hemodynamic toxicity than Tempol, suggesting that rapid oxidation of Tempol-h to Tempol takes place in vivo.
88 citations
TL;DR: Vanillyl alcohol (VA) is a component of Gastrodia elata Bl.
TL;DR: A novel approach to inducing transplant tolerance to islet allografts with IT injection of allopeptide-pulsed host DC is demonstrated and suggests that immunization strategies using DC expressing MHCAllopeptides or peptide analogue might be potentially useful in the treatment of autoimmune diabetes mellitus.
Abstract: Background. As T-cell receptor-major histocompatibility complex (MHC) class I/self peptide interaction regulates T-cell development in the thymus, we reasoned that presentation of peptides by self dendritic cells (DC) to developing T cells in the thymus might induce acquired thymic tolerance. This hypothesis is based on the finding that intrathymic injection of allopeptides in the adult animal induces acquired tolerance. To examine this hypothesis, we studied the effects of intrathymic (IT) injection of a single immunodominant Wistar-Furth (WF) MHC class I (RT1.A u ) peptide-pulsed host DC on islet allograft survival in the WF-to-ACI rat combination. Methods. Bone marrow-derived ACI DC expressing MHC class I and II, OX62, and ED2 present allopeptides to naive and specifically peptide-primed syngeneic T cells in mixed lymphocyte reaction. Host DC pulsed with RT1.A u peptide 5 (residues 93-109) were injected into the thymus of streptozotocin-induced diabetic ACI that were transplanted 7 days later with donor-type (WF) or third-party (Brown Norway [BN]) islets. Results. Whereas IT injection of 300 μg of peptide 5 alone led to normoglycemia and permanent islet survival in three of six diabetic ACI recipients, similar treatment combined with simultaneous intraperitoneal injection of 0.5 ml of anti-lymphocyte serum (ALS) on day -7 led to 100% permanent islet allograft survival (>200 days) compared to a mean survival time of 15.0±2.3 days in controls treated with ALS alone. In contrast, similarly prepared animals rejected the third-party (BN) islets in an acute fashion. To address the question of indirect allorecognition in acquired thymic tolerance, we examined the effect of peptide-pulsed host DC on graft survival. Whereas IT injection of peptide-pulsed host DC alone resulted in permanent islet survival in two of five animals, IT injection of peptide-pulsed host DC combined with 0.5 ml of ALS induced 100% donor-specific permanent islet allograft survival in the WF-to-ACI rat combination. These results suggest that thymic DC take up, process, and present the administered peptide to the developing T cells by the indirect allorecognition pathway in the induction of acquired thymic tolerance. Conclusion. We have demonstrated a novel approach to inducing transplant tolerance to islet allografts with IT injection of allopeptide-pulsed host DC. This finding suggests that immunization strategies using DC expressing MHC allopeptides or peptide analogue might be potentially useful in the treatment of autoimmune diabetes mellitus.
TL;DR: Results suggest that systemic therapy with plasmid DNA complexed with cationic liposomes merits further development as an alternative method for anti-inflammatory treatment of arthritis.
Abstract: A novel formulation of cationic liposomes containing the novel cytofectin ACHx was used for delivery of an anti-inflammatory cytokine gene, IL-10, to mice with established collagen induced arthritis. A single intraperitoneal injection of human IL-10 expression plasmid complexed with liposomes 2 to 4 days after the onset of arthritis was sufficient to give significant and prolonged amelioration of arthritis for 30 days. Preliminary experiments suggested that the therapeutic effect was IL-10 dose-dependent. The distribution of the human IL-10 DNA after injection was widespread, including the inflamed paws. Human IL-10 mRNA was also detected in the paws 24 h after injection. IL-10 protein was below the level of detection in paws and serum but was detected in some tissues up to 10 days after injection. The target cell of transfection was demonstrated to be the macrophage. These results suggest that systemic therapy with plasmid DNA complexed with cationic liposomes merits further development as an alternative method for anti-inflammatory treatment of arthritis.
TL;DR: The results suggest that SAC research may ultimately lead to a resolution of the adverse effects of doxorubicin treatment in cancer chemotherapy, and that heart and liver damage was significantly less severe in SAC treated mice than in mice receiving only doxorbicin.
Abstract: Doxorubicin, a potent anticancer drug, is effective against a wide range of human neoplasms. However, the clinical uses of doxorubicin have been limited due to its serious cardiotoxic effects, which are likely the result of generation of free radicals and lipid peroxidation. S-Allylcysteine (SAC), an organosulfur compound purified from garlic, has been reported to have antioxidant and radical scavenging effects. Thus, we examined the effect of SAC on doxorubicin toxicity in mice. Severe doxorubicin toxicity was induced in mice by a single intraperitoneal injection (15 mg/kg body weight). SAC (30 mg/kg) was injected intraperitoneally daily for 5 days, starting two days prior to the administration of doxorubicin. Body weight was measured every alternate day. A measurement of serum creatine phosphokinase (CPK) and a histopathological analysis of the heart and liver was performed 6 days after the administration of doxorubicin. Death of any of the animals was recorded during the observation period. Doxorubicin injection induced a mortality rate of 58%, with SAC treatment reducing the doxorubicin-induced mortality rate to 30%. The severe body weight loss caused by doxorubicin (13%) was also significantly attenuated by SAC treatment (9%). Although an elevation of the level of serum CPK was observed following doxorubicin injection (5472 +/- 570 i.u./L), treatment with SAC significantly reduced the level of CPK (1923 +/- 635 i.u./L). Histological analysis demonstrated that heart and liver damage was significantly less severe in SAC treated mice than in mice receiving only doxorubicin. These results suggest that SAC research may ultimately lead to a resolution of the adverse effects of doxorubicin treatment in cancer chemotherapy.
TL;DR: The data indicate that continued systemic administration of tumor necrosis factor‐binding protein resulted in significantly weaker wounds with no corresponding differences in wound collagen content, and collagen gene expression, and suggests that tumor necrot factor‐α inhibition throughout healing leads to a qualitatively impaired wound without a quantitative alteration in collagen deposition.
Abstract: Exogenous administration of tumor necrosis factor-alpha has been shown to both enhance and attenuate cutaneous healing in a dose-dependent manner We examined the effects of tumor necrosis factor inhibition in the healing wound by both systemic and local administration of tumor necrosis factor-binding protein Male Balb/C mice underwent dorsal skin incision with subcutaneous implantation of 20 mg polyvinyl alcohol sponges (4 per animal) In Experiment I, one group (n = 20) received intraperitoneal injections of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding, while another group (n = 20) received saline Four animals from each group were euthanized on days 1, 3, 5, 7, and 14 postwounding In Experiment II, one group (n = 10) received an intraperitoneal injection of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding and every third day thereafter Another group (n = 10) received an intraperitoneal injection of saline at the time of wounding and every third day thereafter In Experiment III, one group received a single intraperitoneal injection of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding (n = 7), or on postwounding day 4 (n = 7), or day 7 (n = 7) Another group received saline injections at the time of wounding (n = 7), or on postwounding days 4 or 7 (n = 7, respectively) All animals in Experiments II and III were killed at postwounding day 14 Wound breaking strengths were assessed using a tensiometer Wound fluid collected from the implanted sponges was assayed for tumor necrosis factor-alpha and tumor necrosis factor-binding protein levels using a biological assay and enzyme-linked immunosorbent assay, respectively Collagen gene expression in sponge granulomata was assessed by Northern analysis Collagen deposition in sponges was quantified by measuring hydroxyproline content Wounds were significantly weaker in the animals that received repeated injections of tumor necrosis factor-binding protein with a mean wound breaking strength of 931 g vs 1866 g in controls (p < 005) Wound breaking strength in groups that received a single injection of tumor necrosis factor-binding protein on either day 0, 4, or 7 postwounding were no different than their respective controls There was no difference in the mean hydroxyproline content of sponges between any of the tumor necrosis factor-binding protein groups and their respective controls Northern analysis for collagen I and III expression also revealed no differences These data indicate that continued systemic administration of tumor necrosis factor-binding protein resulted in significantly weaker wounds with no corresponding differences in wound collagen content, and collagen gene expression This suggests that tumor necrosis factor-alpha inhibition throughout healing leads to a qualitatively impaired wound without a quantitative alteration in collagen deposition
TL;DR: Intraperitoneal therapy with taurolidine and the combination with heparin inhibits the intraperitoneal tumour growth and trocar recurrences.
Abstract: Background: Recent clinical and experimental studies investigated the problem and possible pathomechanisms of port-site metastases after laparoscopic resection of malignant tumours. A generally accepted approach to prevent these tumour implantations does not exist so far. Methods: After subcutaneous and intraperitoneal injection of 104 cells of colon adenocarcinoma (DHD/K12/TRb) the influences of either taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumour growth were investigated in 105 rats undergoing laparoscopy with carbon dioxide. The animals were then randomised into seven groups. A pneumoperitoneum was established using carbon dioxide for 30 min (8 mmHg). Three incisions were used: median for the insufflation needle, and a right and left approach in the lower abdomen for trocars. To investigate the intraperitoneal (local) influence of either taurolidine and heparin on tumour growth the substances were instilled intraperitoneally. Systemic effects were expected when the substances were applied intravenously (iv). Synergistic influences were tested when both application forms were combined. The number and the weight of tumours as well as the incidence of abdominal wall and port-site metastases were determined four weeks after intervention. Blood was taken to evaluate the influences of taurolidine and heparin on systemic immunologic reactions: seven days before laparoscopy, two hours, two days, seven days, and four weeks after operation, and the peripheral lymphocytes were determined. Results: Intraperitoneal (ip) tumour weight in rats receiving taurolidine (median 7 mg) and taurolidine/heparin (0 mg) intraperitoneally was significantly reduced when compared to the control group (52 mg) (P=0.001). There was no difference of subcutaneus tumour growth among the groups (P=0.4). Trocar recurrences were decreased when taurolidine was applied ip (3/15), ipiv (4/15), and ip in combination with heparin (4/15) in comparison to the control group (10/15). Immediately after intervention treated and untreated groups showed a peripheral lymphopenia. Conclusions: The intraperitoneal therapy with taurolidine and the combination with heparin inhibits the intraperitoneal tumour growth and trocar recurrences. Neither the intraperitoneal nor the systemic application or the combination of taurolidine and heparin did reduce the subcutaneous tumour growth. The intervention caused a lymphopenia which was compensated on day two.
TL;DR: A significant reduction in pulmonary oedema following in vivo gene transfer is demonstrated and raises the possibility of gene therapy as a novel, localised approach for pulmonary Oedema in clinical settings such as ARDS and lung transplantation.
Abstract: Resolution of pulmonary oedema is mediated by active absorption of liquid across the alveolar epithelium. A key component of this process is the sodium-potassium ATPase (Na+K+-ATPase) enzyme located on the basolateral surface of epithelial cells and up-regulated during oedema resolution. We hypothesised that lung liquid clearance could be further up-regulated by lipid-mediated transfer and expression of exogenous Na+K+-ATPase cDNA. We demonstrate proof of this principle in a model of high permeability pulmonary oedema induced by intraperitoneal injection of thiourea (2.5 mg/kg) in C57/BL6 mice. Pretreatment of mice (24 h before thiourea) by nasal sniffing of cationic liposome (lipid #67)–DNA complexes encoding the α and β subunits of Na+K+-ATPase (160 μg per mouse), significantly (P < 0.01) decreased the wet:dry weight ratios measured 2 h after thiourea injection compared with control animals, pretreated with an equivalent dose of an irrelevant gene. whole lung na+K+-ATPase activity was significantly (P < 0.05) increased in mice pretreated with na+K+-ATPase cDNA compared both with untreated control animals as well as animals pretreated with the irrelevant gene. Nested RT-PCR on whole lung homogenates confirmed gene transfer by detection of vector-specific mRNA in three of four mice studied 24 h after gene transfer. This demonstration of a significant reduction in pulmonary oedema following in vivo gene transfer raises the possibility of gene therapy as a novel, localised approach for pulmonary oedema in clinical settings such as ARDS and lung transplantation.
TL;DR: The inflammatory effects of respirable cellulose fibres were studied in two short‐term animal models: intraperitoneal injection in mice, and inhalation in rats.
Abstract: The inflammatory effects of respirable cellulose fibres were studied in two short-term animal models: intraperitoneal injection in mice, and inhalation in rats.
The mouse peritoneal cavity is particularly sensitive to fibrous compared to non-fibrous particles. Both cellulose fibres and the positive control fibre, crocidolite asbestos, were administered in doses ranging from 104 to 108 fibres and caused marked, dose-dependent recruitment of inflammatory cells to the mouse peritoneal cavity, which was highest 1 day following injection. Crocidolite was much more active than cellulose, despite the mass dose of cellulose being 66 times greater for an equivalent number of fibres. Crocidolite at the higher doses caused inflammation to persist through 7 days.
For the inhalation study, rats were exposed daily, 5 days per week, to aerosols of cellulose dust for ca. 3 weeks at a concentration of 1000 fibres ml−1. Inhalation exposure induced an early inflammatory response in rat lungs, as determined by bronchoalveolar lavage, which peaked at 1 day following the start of inhalation and thereafter declined, despite a further 13 days of exposure over a period of 18 calendar days. In vitro production of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α) by lavaged alveolar macrophages was markedly depressed by the end of the exposure period in cellulose-exposed animals, compared to sham-exposed controls, and this effect was still present in rats that had been allowed to recover for 28 days beyond the end of exposure.
We conclude that the cellulose material studied is less inflammogenic than crocidolite and that the extent of the inflammatory response within the lung appears to reduce with continued exposure over a 14-day period. Copyright © 2000 John Wiley & Sons, Ltd.
Journal Article•
TL;DR: Systemic or conjunctival administration of ISS- ODN was shown to significantly inhibit allergic responses in this mouse model, indicating that ISS-ODN may be an effective form of immunotherapy for this class of allergic disease.
Abstract: PURPOSE. To evaluate the therapeutic potential of immunostimulatory sequence oligodeoxynucleotides (ISS-ODN) administration in ocular allergy, using a mouse model of ragweed-specific conjunctivitis. METHODS. A murine model of allergic conjunctivitis involving SWR/J mice sensitized and challenged with short ragweed was used to test immunostimulatory DNA sequences for therapeutic potential. ISS-ODN or control ODN (0.1 mg/mouse) was administered intraperitoneally or topically to the conjunctiva 3 days before final allergen challenge. Multiple parameters of clinical symptoms evident during the acute-phase reaction and the cellular components of the late-phase reaction were evaluated in both groups of mice. RESULTS. All parameters of clinical symptoms were markedly inhibited after intraperitoneal injection of ISS-ODN, whereas topical application to the conjunctiva did not inhibit clinical symptoms significantly. Remarkably, a single topical treatment with ISS-ODN (as well as by intraperitoneal injection) completely inhibited both eosinophilia and neutrophilia in the late-phase reaction. CONCLUSIONS. Systemic or conjunctival administration of ISS-ODN was shown to significantly inhibit allergic responses in this mouse model. This indicates that ISS-ODN may be an effective form of immunotherapy for this class of allergic disease.
TL;DR: The results suggest that administration of exogenous surfactant may play a role in the treatment of patients poisoned with paraquat and that immediate intratracheal administration of Survanta after paraquats injection tended to increase the survival rate on d 1 compared to rats without SurvantA administration.
Abstract: In a rat model of paraquat-induced lung injury, pulmonary alveolar lavage fluid metabolic parameters were assessed to establish damage, and the use of surfactant was employed as a protective agent. Three groups of adult male Sprague-Dawley rats received intraperitoneal injection of paraquat (35 mg/kg body weight) in 1 ml saline, or received 1 ml saline, or no material. On d 3, 7, 14, and 21 after injection, pressure-volume curves and pulmonary alveolar lavage fluids were obtained. On d 3 paraquat significantly increased the lung wet/dry weight ratio and protein content but lowered phosphatidylcholine levels. There were no marked changes at other time points in the parameters examined. The pressure-volume curves initially moved downward and to the right on d 3 and 7 and then returned to control levels in the paraquat-treated rats. Immediate intratracheal administration of Survanta after paraquat injection (70 mg/kg body weight) tended to increase the survival rate on d 1 compared to rats without Survanta a...
TL;DR: Investigation of thallium in the body and its toxic effect on the histology and function of the liver and kidney of rats after Tl administration found the content of Tl was found to be highest in the kidney, followed by ileum, stomach and liver.
TL;DR: The results suggest that the transgenic rats, whose GH secretion is suppressed, develop obesity due to early onset of an increase in food intake and a decrease in locomotor activity with leptin resistance resulting from deteriorating leptin transport from peripheral blood to cerebrospinal fluid.
Abstract: Background: Human growth hormone (hGH) transgenic (TG) rats have been produced in our laboratory. These TG rats are characterized by low circulating hGH levels, virtually no endogenous rGH secretion, and massive obesity. Objective: To elucidate how energy balance and leptin sensitivity contributed to the establishment of this obesity. Design and methods: Food intake, locomotor activity and leptin concentrations in serum and cerebrospinal fluid were measured in TG rats and their non-transgenic littermates (control). The effect of intraperitoneal and intracerebroventricular injection of leptin on food intake and body weight gain was also examined. Results: An increase in food intake and a decrease in locomotor activity were observed from 4 and 7 weeks of age, respectively, in the transgenic rats compared with control. Serum leptin concentrations of the transgenic rats were more than twice as high as those of control rats and were associated with an increased white adipose tissue mass and ob gene expression. Intraperitoneal injection of leptin significantly decreased food intake and body weight gain in control rats, but not in transgenic rats. Leptin concentration in the cerebrospinal fluid of transgenic rats was not different from that of control rats, and intracerebroventricular injection of leptin was similarly effective in reducing food intake and body weight gain as it was in control rats. Conclusions: These results suggest that the transgenic rats, whose GH secretion is suppressed, develop obesity due to early onset of an increase in food intake and a decrease in locomotor activity with leptin resistance resulting from deteriorating leptin transport from peripheral blood to cerebrospinal fluid.
TL;DR: The results suggest that plant tannins administered topically or injected intraperitoneally reduce the tumor-promoting effects of UV-B radiation and thus could be useful photoprotectants.
Abstract: We recently showed that Tarapod tannic acid (TA), a hydrolyzable tannin extracted from the pods of the Tara tree (Caesalpinia spinosa), was more effective than other tannins tested at inhibiting ultraviolet-B (UV-B)-stimulated hydrogen peroxide activity (an indirect measure of free radicals) in the skin of hairless mice. We also found that Tarapod TA inhibited UV-B-induced ornithine decarboxylase activity and UV-B-stimulated DNA synthesis, two biochemical markers linked to the skin tumor-promoting ability of this physical carcinogen. For this reason, we examined the effect of topical application, force feeding (gavage), and intraperitoneal injections of Tarapod TA on mouse skin chronically treated with UV-B light. Mice were initiated by a single topical application of 7,12-dimethylbenz[a]anthracene (50 nmol) and promoted by two weekly treatments with UV-B light (250 mJ/cm2) for 25 weeks. Topical application of Tarapod TA, 20 minutes before irradiation, resulted in a dose-dependent inhibition of tumor incidence (number of mice with tumors) and tumor yield (number of tumors/mouse), with 8 mg of TA inhibiting tumor yield by 70% at Week 25. Intraperitoneal injections of low doses (10 mg/kg mouse body wt), but not of high doses (25 mg/kg body wt), of TA afforded protection against UV-B-induced papillomas. However, the protection by intraperitoneal injection was lower than that observed by topical application: 10 mg/kg body wt of TA reduced tumor yield by 55%. The force feeding of 10 mg of Tarapod TA before irradiation failed to significantly inhibit the yield of tumors at the end of the experiment but delayed tumor appearance by six weeks. These results suggest that plant tannins administered topically or injected intraperitoneally reduce the tumor-promoting effects of UV-B radiation and thus could be useful photoprotectants.
TL;DR: Data suggests that NO has a GABA-T-inhibiting role in the brain, and that NO-decreasing action of l -NAME coincided with a reduction in the concentration of GABA and an enhancement of GABA- T activity.
TL;DR: In this article, the authors evaluated the effect of multiple injections of the herpes simplex virus thymidine kinase in an adenovirus vector and ganciclovir on survival in a murine model of human epithelial ovarian cancer.
TL;DR: The results of the present study indicate that rML has potent anti-tumour activity, if administered locally into the peritoneum of a human ovarian cancer harbouring SCID mouse, and clinical studies with post-operative instillation of rML in ovarian cancer patients should be encouraged to provide clinical evidence for the effectiveness of the rML treatment.
TL;DR: The first peak might play a role in UA-induced tubular damage, while the second one might represent the removal of excess regenerating cells during the recovery phase, which might be involved in the acquired resistance to rechallenge injury by UA.
TL;DR: In this particular model of ARDS the monoclonal antibody against the CD11-CD18 complex had a beneficial effect, reducing PMN infiltration and oxygen radical release in the lungs, preventing alveolocapillary membrane damage, improving gas exchange and, finally, significantly reducing mortality.
Abstract: Acute lung injury is frequent after severe peritonitis. The aim of this study was to investigate whether inhibition of the adhesion molecule CD11-CD18 on polymorphonuclear leukocytes (PMNs) would have any beneficial effects on pulmonary function and mortality in an animal model reproducing these clinical conditions. Acute peritonitis was induced in 36 rabbits by intraperitoneal injection of zymosan (0.6 g/kg) suspended in mineral oil; 20 were pretreated with a murine-specific IgG2a anti-CD18 monoclonal antibody, 16 (controls) with nonspecific purified murine IgG (1 mg/kg). The animals were followed for 10 d, then killed for histologic examination of the lungs. Blood samples were taken on Days 0, 1, 3, 7, and 10 for red blood cell (RBC), white blood cell (WBC), and platelet counts, pH, Po 2, Pco 2, carbon dioxide content (HCO3 −) measurements, and renal and liver tests. Treatment with the anti-CD18 monoclonal antibody reduced mortality by approximately 40% (p < 0.05). Po 2 was higher in these treated anima...
TL;DR: The SD rat may be a suitable model for future fMRI studies of the hypothalamus involving the administration of exogenous nutrients and medications, and a significant acute transient decrease in the fMRI signal intensity is demonstrated.
Abstract: The hypothalamic functional MRI (fMRI) response in an animal model was studied following energy intake. Six fasted (12 h) Sprague-Dawley (SD) rats were administered an intraperitoneal injection of glucose (0.72 grams/kg body weight), while a mid-sagittal slice through the hypothalamus was continuously imaged for 60 min using a conventional T2*-weighted gradient-echo sequence. All rats demonstrated a significant acute transient decrease in the fMRI signal intensity (mean: 3.4%) in the hypothalamic region within 12-16 min after intraperitoneal glucose injection. The SD rat may be a suitable model for future fMRI studies of the hypothalamus involving the administration of exogenous nutrients and medications.
TL;DR: Results demonstrate that the blockade of intraperitoneal interleukin-1β-induced fever after subdiaphragmatic vagotomy cannot be accounted for by alterations of interleucin- 1β levels in the general circulation.
Abstract: Peripheral interleukin-1β has been implicated in the initiation of fever responses, yet the pathways by which it influences brain function are still unclear. Sectioning the abdominal vagus has been reported to inhibit fever after intraperitoneal administration of interleukin-1β, suggesting that vagal afferents participate in signaling the brain to mount a fever response to interleukin-1β. However, the inhibitory effect of subdiaphragmatic vagotomy could be due to alterations in pharmacokinetics such that the intraperitoneally injected cytokine does not reach the general circulation in sufficient quantities to activate the brain via blood-borne signaling. We measured both fever and plasma levels of interleukin-1β in vagotomized and sham-operated rats after intraperitoneal administration of 1 μg/kg human recombinant interleukin-1β to determine whether vagotomy reduces fever and levels of circulating interleukin-1β after intraperitoneal injection. Plasma levels of human recombinant and endogenous rat interleukin-1β were measured in separate enzyme-linked immunosorbent assays. While intraperitoneal administration of human recombinant interleukin-1β elevated plasma levels of this cytokine similarly in vagotomized and sham-operated animals, only sham-operated rats responded with fever. Plasma levels of endogenous rat interleukin-1β were unchanged by any treatment. These results demonstrate that the blockade of intraperitoneal interleukin-1β-induced fever after subdiaphragmatic vagotomy cannot be accounted for by alterations of interleukin-1β levels in the general circulation.