Search PubMed⌕ Search

Biomedical subjects

A Ialenti

Publications and source records attributed to A Ialenti.

35 records · Page 2Linked to original sources
PubMed1996

Synthesis and antinociceptive activity of peptides related to interleukin-1 beta 193-195 Lys-Pro-Thr.

To obtain information about the structure-activity relationships of analgesic peptides, we modified the previously reported tripeptide, H-Lys-Pro-Thr-OH (C). The proline part in C was replaced with various analogues of unconventional amino acids [(3aS, 7aS)-octahydroindole-2-carboxylic acid (Oic), (S,S,S,)-2-azabiciclo [3.3.0]octane-3-carboxylic acid (Aoc), D-Aoc, and (2S, 4R)-hydroxyproline (Hyp)] with varying lipophilic, steric, and conformational properties, and alternatively with Lys and Orn in the lysine part. Moreover, the threonine part was changed to various natural amino acids (Ser, Thr, Val, Leu). All the compound were screened in vivo for their analgesic effects in mouse writhing test. Compound 24 (H-Orn-Hyp-Val-OH), the most active compound within the series, showed an ED50 value of 10 mg/kg, which is comparable with the ED50 values exhibited by indometacin (4.1 mg/kg) and the dipeptide H-Lys-D-Pro-OH (6.9 mg/kg), both used as reference drugs.

Acetic Acid↗
PubMed1995

Endogenous nitric oxide increases prostaglandin biosynthesis in carrageenin rat paw oedema.

The influence of endogenous nitric oxide (NO) on prostaglandin biosynthesis in rat carrageenin oedema was studied. Oedema formation and prostaglandin E2 generation in the inflamed paw were both increased by L- but not D-arginine and reduced by the NO synthase inhibitor, L-NG-nitro arginine methyl ester, and the NO scavenger, haemoglobin. Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. These results suggest that endogenous NO modulates carrageenin oedema by increasing prostaglandin biosynthesis at the inflammatory site through a cGMP-independent mechanism.

Animals↗
PubMed1995

Modulation by nitric oxide of prostaglandin biosynthesis in the rat.

1. Modulation of prostaglandin biosynthesis in vivo by either exogenous or endogenous nitric oxide (NO) has been studied in the rat using arachidonic acid (AA)-induced paw oedema and measuring both the foot volume and the amount of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), in the oedematous fluid recovered from inflamed paws. 2. Paw injections of 150 or 300 nmol of AA were virtually inactive whereas 600 nmol produced a moderate oedema which was greatly reduced by the NO synthase inhibitor L-NG-nitro arginine methyl ester (L-NAME, 100 nmol/paw) and the NO scavenger haemoglobin (Hb, 30 mumol/paw), but unaffected by the inhibitor of the soluble guanylate cyclase, methylene blue (Mb, 3 mumol/paw) and L-arginine (15 mumol/paw). 3. The NO-donors (10 mumol/paw) 3-morpholino-sydnonimine-hydrochloride (SIN-1), S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and sodium nitroprusside (SNP) significantly potentiated the paw oedema induced by AA (300 nmol/paw). 4. SIN-1 (2.5, 5 and 10 mumol/paw) produced a significant dose-dependent increase of the oedema induced by AA which was correlated with increased amounts of 6-keto-PGF1 alpha in the fluid recovered from inflamed paws. 5. Both oedema and prostaglandin biosynthesis induced by the combination AA+SIN-1 were greatly suppressed by either Hb (30 mumol/paw) or indomethacin (3 mumol/paw or 5 mg kg-1 s.c.) but unaffected by Mb (3 mumol/paw). 6. In LPS-treated rats (6 mg kg-1, i.p.) doses of AA inactive in normal animals produced a remarkable oedema which was reduced by L-NAME or Hb, unaffected by Mb and increased by L-arginine.7. These results demonstrate that NO increases prostaglandin biosynthesis in vivo through a guanosine 3': 5'-cyclic monophosphate (cyclic GMP)-independent mechanism and suggest that the interaction between NO synthase and cyclo-oxygenase (COX) pathways may represent an important mechanism for the modulation of the inflammatory response.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Hyaluronic acid modulates acute and chronic inflammation.

We have studied the effect of hyaluronic acid (HA) in two standard models of acute and chronic inflammation in the rat, i.e. carrageenin oedema and adjuvant arthritis. Our results show that HA was able to inhibit, in a dose-related fashion, both types of inflammatory reactions. These findings suggest that HA may have a modulatory role in the inflammatory process and may explain, at least in part, the protective role of HA in the inflammatory cartilage damage.

Acute Disease↗
PubMed1993

Structural characterization of a biologically active human lipocortin 1 expressed in Escherichia coli.

Lipocortin or annexin 1 is a calcium-dependent phospholipid-binding protein which probably acts as a glucocorticoid- regulated anti-inflammatory factor. cDNA for human lipocortin 1 was cloned in the pT7.7 expression plasmid under the control of the inducible bacteriophage T7 RNA polymerase promoter. Upon induction with isopropyl thio-beta-D-galactoside, large amounts of the protein were produced and accumulated in Escherichia coli in a soluble form. The recombinant protein was purified to homogeneity by means of two subsequent ion-exchange chromatographic steps. The final yield was about 30 mg/l bacterial culture. Electrospray mass spectrometric analysis of the purified protein demonstrated that the recombinant product corresponds to the native human lipocortin 1, without the initial methionine and with a free N-terminal alanine; tryptic peptide mapping by fast-atom-bombardment mass spectrometry showed that the recombinant protein contains cysteine residues at positions 263 and 324 with free thiol groups, whereas Cys270 and Cys343 are probably involved in an intrachain disulfide bridge. Recombinant human lipocortin 1 reduces the carrageenin-induced paw oedema in rat in vivo and inhibits porcine pancreatic phospholipase A2 activity in vitro; in both cases, a dose-related response is observed.

Amino Acid Sequence↗
PubMed1993

Modulation of adjuvant arthritis by endogenous nitric oxide.

1. The role of endogenous nitric oxide (NO) in adjuvant arthritis in Lewis rats has been studied by use of L-arginine, the amino acid from which NO is synthesized, and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Prolonged modulation (35 days) of the L-arginine: NO pathway in rats was achieved by dissolving test compounds in the drinking water (L-arginine: 3, 10 and 30 mg ml-1; L-NAME: 0.1, 1 and 10 mg ml-1). 2. Arthritis was exacerbated by L-arginine and suppressed by L-NAME in a dose-related fashion. Combined treatment with L-NAME (1 mg ml-1) and L-arginine (30 mg ml-1) did not modify the arthritis. 3. Reduced weight gain, which is a feature of adjuvant arthritis, was modified by these compounds so that L-arginine reduced weight gain whereas L-NAME increased weight gain compared with that in control animals. 4. D-Arginine (30 mg ml-1), NG-nitro-D-arginine methyl ester (D-NAME: 1 mg ml-1) and L-lysine (30 mg ml-1), an amino acid not involved in the generation of NO, were without effect on either arthritis or body weight gain. 5. Antigen-stimulated proliferation of T-lymphocytes as well as generation of nitrite (NO2-) and release of acid phosphatase from macrophages were all enhanced in L-arginine-treated arthritic rats and reduced in L-NAME-treated animals. 6. These results suggest that endogenous NO modulates adjuvant arthritis, possibly by interfering with the activation of T-lymphocytes and/or macrophages.

Acid Phosphatase↗
PubMed1992

Modulation of acute inflammation by endogenous nitric oxide.

The role of endogenous nitric oxide (NO) in acute inflammation was investigated using two inhibitors of NO synthase (NG-nitro-L-arginine methyl ester(L-NAME) and NG-monomethyl-L-arginine (L-NMMA)) as well as L- or D-arginine. The effect of test compounds was studied on the carrageenin-induced increase in vascular permeability in rat skin and in dextran- and carrageenin-induced paw oedema. Both L-NAME and L-NMMA dose dependently inhibited the increase in vascular permeability and oedema formation. L- but not D-arginine increased these inflammatory responses and reversed the inhibitory effects of L-NAME and L-NMMA. In dexamethasone-treated rats L-arginine enhanced the dextran-induced oedema and the early phase of carrageenin-induced oedema but did not modify the inhibition by dexamethasone of the late phase of carrageenin-induced oedema. These results suggest that endogenous NO is released at the site of acute inflammation and modulates oedema formation. Depending on the time course or on the type of inflammation, NO may be predominantly generated by the constitutive or by the inducible NO synthase.

Acute Disease↗
PubMed1992

Lipocortin and vasocortin: two species of anti-inflammatory proteins mimicking the effects of glucocorticoids.

The anti-inflammatory effect of glucocorticoids depends, at least in part, on the induction of two regulatory proteins, lipocortin and vasocortin, both preventing the release of inflammatory mediators. Lipocortin inhibits phospholipase A2 (PLA2) and therefore reduces arachidonic acid metabolites formation. Vasocortin inhibits histamine release from mast cells. Lipocortin and vasocortin may be regarded as the first two identified members of the (perhaps greater) family of glucocorticoid-induced proteins.

Animals↗
PubMed1989

Selective inhibition by vasocortin of histamine release induced by dextran and concanavalin-A from rat peritoneal cells.

Vasocortin, a glucocorticoid-induced anti-inflammatory protein, has been purified from the peritoneal lavage fluid of dexamethasone-treated rats. Vasocortin inhibited the release of histamine from rat peritoneal cells stimulated by dextran or concanavalin A but did not alter the release induced by calcium ionophore A23187 or compound 48/80. This selective effect exhibited by vasocortin mimics the glucocorticoid inhibition of histamine release from rat mast cells.

Animals↗
PubMed1986

Glucocorticoid induction of angiotensin converting enzyme.

Angiotensin converting enzyme (ACE) converts angiotensin I (Angio I) to angiotensin II (Angio II) and inactivates bradykinin (BK). Glucocorticoids in the physiological range increase ACE in rabbit alveolar macrophages and bovine endothelial cells in culture. Since Angio I and BK are cleaved by ACE catalysis during passage through the pulmonary vasculature we have studied the steroid modulation of ACE in the rat lung. The conversion of Angio I to Angio II by isolated lungs from normal or adrenalectomized male Wistar rats has been evaluated. The initial conversion of Angio I to Angio II in lungs from normal rats was about 60%. In contrast the initial converting activity in lungs from adrenalectomized rats was about 30%. In both groups the converting activity progressively decreased. After 3 h it was about 30% in normal lungs and virtually undetectable in lungs from adrenalectomized rats. Dexamethasone infusion (1 microgram/ml) prevented the decrease in ACE activity observed in normal lungs and induced a gradual enhancement of converting activity in lungs from adrenalectomized animals up to the control level. The effect of dexamethasone was abolished by simultaneous infusion of cycloheximide (1 microgram/ml). These results demonstrate that glucocorticoids induce ACE synthesis in the rat lung. By this induction glucocorticoids promote the increase of both Angio II formation and BK degradation. Thus ACE induction may represent a possible mechanism whereby glucocorticoids might control vascular tone and permeability according to the general mode of action of steroid hormones.

Adrenalectomy↗
PubMed1985

The anti-inflammatory effect of glucocorticoid-induced phospholipase inhibitory proteins.

The anti-inflammatory effect of glucocorticoids has been investigated in two standard models of experimental inflammation, i.e. rat paw oedema induced by carrageenin or dextran. Both types of oedema are suppressed by dexamethasone while indomethacin and BW755C only suppress carrageenin oedema. Dexamethasone inhibits dextran oedema according to the accepted mode of action of steroid hormones since the inhibition occurs after a 2-3 h time lag and is abolished by pretreating animals with actinomycin D. Dextran oedema and carrageenin oedema are also controlled by endogenous corticoids since adrenalectomy potentiates the paw oedema formation induced by low concentrations of phlogogenic agents. It has been shown that glucocorticoids induce both in vitro and in vivo the formation and release of antiphospholipase proteins which are anti-inflammatory in that they greatly suppress carrageenin oedema. However, these proteins have no effect on dextran oedema. We conclude that the inhibition of dextran oedema by glucocorticoids depends on the formation of another type of anti-inflammatory protein.

Animals↗