Apc-driven colon carcinogenesis in Pirc rat is strongly reduced by polyethylene glycol.

Polyethylene glycol (PEG) is one of the most powerful agents in reducing chemically induced carcinogenesis in rat colon. However, contrasting results in Min mice dampened the enthusiasm on this potentially strong and virtually safe, cancer chemopreventing agent. Pirc (F344/NTac-Apc (am1137) ) rats carrying a germline heterozygous mutation in the Apc gene, spontaneously develop multiple tumours in the colon thus modelling both familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC).

Inhibition of interleukin-1 beta-induced pyresis in the rabbit by peptide 204-212 of lipocortin 5.

The intracerebroventricular administration of interleukin-1 beta (12.5 ng/kg) in rabbits caused a prompt rise of prostaglandin E2 concentration (+ 632.6 +/- 243.

Increase of extracellular brain calcium involved in interleukin-1 beta-induced pyresis in the rabbit: antagonism by dexamethasone.

1. This study investigates the role of extracellular brain calcium in the hyperthermia induced by interleukin-1 beta (IL-1 beta). 2.

4-substituted-5-acetyl-2-methyl-6-phenyl-3(2H)pyridazinones as PGE2 and IL-1 release inhibitors from mouse adherent macrophages.

A series of 4,5-functionalized 3(2H)-pyridazinones were evaluated as prostaglandin E2 (PGE2) and interleukin-1 (IL-1) release inhibitors from mouse adherent macrophages. Among the tested compounds only 2b was found to be devoid of activity in both the PGE2 and IL-1 tests, whereas the other compounds, showed a significant dose-dependent activity. Compounds 2a, 3 and 4 were able to inhibit PGE2 better than IL-1 release from stimulated macrophages.

Conceivable difference in the anti-inflammatory mechanisms of lipocortins 1 and 5.

Human recombinant lipocortins (LCT) 1 and 5 have been expressed in a yeast secretion vector and purified by ion exchange chromatography. The action of the proteins has been investigated in two models of experimental acute inflammation in the rat: carrageenin induced paw oedema and zymosan induced pleurisy. The effects of the proteins on PGE(2) release in vitro by rat macrophages stimulated with zymosan and on rat neutrophil chemotaxis induced by FMLP have also been assessed.

Inhibition of smooth muscle contraction and platelet aggregation by peptide 204-212 of lipocortin 5: an attempt to define some structure requirements.

Peptide 204-212 of lipocortin (LC) 5 inhibited porcine pancreatic phospholipase A(2) (PLA(2)) induced rat stomach strip contractions and ADP induced rabbit platelet aggregation in a concentration dependent manner (IC(30) of 10 muM and 400 muM, respectively). The first two amino acids are not necessary since the eptapeptide 206-212 was equipotent in both assays (IC(30) of 12.5 muM and 420 muM).

Prostaglandin E2 and bacterial lipopolysaccharide stimulate bioactive interleukin-1 release from rat hypothalamic explants.

While interleukin-1 (IL-1) is intimately involved in locally modulating the acute inflammatory response, it is also able to influence processes at remote sites, i.e., in an endocrine manner.

Anti-inflammatory effect of tuftsin and its retro-inverso analogue in rat adjuvant arthritis.

Tuftsin, an immunostimulating tetrapeptide derived from immunoglobulin heavy chain, and its retro-inverso analogue have been tested in rat adjuvant arthritis. The secondary lesion of rats injected with Freund's adjuvant was significantly inhibited by both the natural and retro-inverso tuftsin administered orally. The retro-inverso analogue was at least tenfold more potent than the parent molecule, suggesting an increased stability to degradation, because of its molecular modification.

Immunostimulation by a partially modified retro-inverso-tuftsin analogue containing Thr1 psi[NHCO](R,S)Lys2 modification.

The tuftsin retro-inverso analogue H-Thr psi[NHCO](R,S)Lys-Pro-Arg-OH was synthesized through a novel procedure for the high-yield incorporation of isolated retro-inverso bonds into peptide chains and the use of the new Meldrum's acid derivative (CH3)2C(OCO)2CH(CH2)4NHCOCF3 followed by its efficient coupling in solution to trimethylsilylated H-D-Thr(t-Bu)NH2. Closely related peptide impurities were eliminated both from the crude final peptide and the fully protected tetrapeptide amide precursor via ion-exchange and reversed-phase displacement chromatography, respectively. The tuftsin retro-inverso analogue proved to be completely resistant to enzymatic degradation in vitro, either against isolated aminopeptidases or human plasma proteolytic enzymes.

Evidence that interleukin-1 and lipoxygenase metabolites mediate the lethal effect of complete Freund's adjuvant in adrenalectomized rats.

Injection of complete Freund's adjuvant (CFA) into the right hind paw of adrenalectomized (ADX) rats caused a lethal effect, maximal after 3 days. Treatment of animals with polyclonal sera raised against either murine recombinant (mr) IL-1 alpha or mrIL-1 beta gave significant protection, suggesting the involvement of this cytokine in the observed lethality. Death was also caused by the intravenous injection of human recombinant (hr) IL-1 beta in ADX rats.

A novel anti-inflammatory peptide from human lipocortin 5.

1. A novel anti-inflammatory peptide (residues 204-212) of human recombinant lipocortin 5 (hrLC5) found on the high similarity region with uteroglobin is described. 2.

Persistent effects of interleukin-1 on smooth muscle preparations from adrenalectomized rats: implications for increased phospholipase-A2 activity via stimulation of 5-lipoxygenase.

Human recombinant interleukin-1 beta (hrIL-1 beta) potentiated CaCl2-induced contractions of isolated stomach strip preparations from adrenalectomized rats (ADXSS). Associated with this effect were increased prostaglandin E2 and peptidyl leukotriene (LT) synthesis. Unlike preparations from normal rat stomach strips or sham-operated animals, tissue responses and eicosanoid production of ADXSS failed to return to pre-hrIL-1 beta control levels after washout of the interleukin, these effects being abrogated by the lipoxygenase inhibitor nordihydroguaiaretic acid.

Metabolic behavior and distribution of the synthetic nonapeptide fragment 163-171 of human IL-1 beta.

The pharmacokinetic parameters and distribution of the adjuvant synthetic nonapeptide VQGEESNDK, corresponding to the fragment in position 163-171 in human IL-1, were analyzed after administration to rabbit through different routes. The radiolabeled peptide did not bind to plasma proteins and, when inoculated i.v.

The effect of adrenalectomy on interleukin-1 release in vitro and in vivo.

1 Peritoneal macrophages (M phi) collected from adrenalectomized (ADX) rats released more interleukin-1 (IL-1) activity and prostaglandin E2 (PGE2) than macrophages from sham-operated (SHO) rats. 2 The increase in IL-1 activity in the supernatants was confirmed by the increase of the cell-associated 33 kD IL-1 alpha precursor in ADX macrophages stimulated by lipopolysaccharide (LPS). 3 After the injection of Complete Freund's Adjuvant (CFA) to induce adjuvant arthritis, 60% of the ADX rats died, while no deaths occurred in the SHO group.

The release of interleukin-1-like activity by macrophages in two models of immunological inflammation in the rat.

Interleukin-1 (IL-1) is a putative mediator of inflammation released by activated macrophages in vitro. The IL-1 release by rat macrophages collected either from exudates in pertussis-induced air pouches or from the peritoneum during adjuvant arthritis has been investigated. In air pouch inflammation LPS-stimulated macrophages collected from sensitized animals release more IL-1 than cells from control rats at day 6 after challenge.

Pharmacokinetics of flunitrazepam in rats studied by a radioreceptor assay.

In rat the kinetics of flunitrazepam (FNZ) was evaluated by a radioreceptor assay (RRA) after i.v. administration of 1 mg/kg and after oral administration of 1 and 3 mg/kg.