PubMed Health⌕ Search

Biomedical subjects

L Raimondi

Publications and source records attributed to L Raimondi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Apoptosis induced by sulindac sulfide in epithelial and mesenchymal cells from human abdominal neoplasms.

We investigated whether the therapeutic action of sulindac, used for the treatment of familial adenomatous polyposis, desmoid tumors, and against colon cancer, could be mediated by its active metabolite, sulindac sulfide, in cell growth and apoptosis on cell lines derived from abdominal neoplasms. Sulindac sulfide actions on cell growth and apoptosis were evaluated in epithelial human colon tumor 8 (HCT8) cell line and mesenchymal cell lines (bovine bone endothelial (BBE) cell line, desmoid tumor-derived cells, human colorectal cancer-derived fibroblasts). Sulindac sulfide (0.1-60 microg/ml) induced a dose-dependent inhibition of cell proliferation of all cell lines tested. Apoptosis was induced at doses of 20 and 40 microg/ml, respectively, in BBE and HCT8 cells with no effect on desmoid tumor cells and colorectal cancer-derived fibroblasts. Since mesenchymal cells respond to clinically effective concentrations of the compound, its preferential action on the stromal compartment of intestinal polyps, desmoid tumors and colon cancer can be proposed, with consequent regression of the tumor.

Abdominal Neoplasms↗
PubMed1998

H1(0) RNA-binding proteins specifically expressed in the rat brain.

During brain maturation, histone H1(0) accumulates in both nerve and glial cells. The expression of this "linker" histone, the role of which still remains unclear, is a complex process, having both transcriptional and post-transcriptional regulatory components. In particular, the expression of H1(0) in rat cortical neurons is regulated mainly at the post-transcriptional level, and unknown cellular proteins are likely to affect H1(0) mRNA stability and/or translation. In looking for such factors, we tested the ability of rat brain extracts to protect H1(0) RNA probe from degradation by T1 RNase. The results reported here demonstrate that rat brain contains at least one major (p40) and two minor (p110 and p70) binding factors, specific for H1(0) RNA, all of which are much more or exclusively expressed in adult rat brain, when compared with other tissues. The binding of the factors is confined to a portion of the 3'-untranslated region (3'-UTR), which is highly conserved among murine and human H1(0) mRNAs. These findings suggest that the proteins identified play a critical role in regulating the expression of H1(0) histone in the brain of mammals.

Animals↗
PubMed1997

Simulation of protein-sugar interactions: a computational model of the complex between ganglioside GM1 and the heat-labile enterotoxin of Escherichia coli.

The cholera toxin from Vibrio cholerae (CT) and the 80% homologous heat-labile toxin of Escherichia coli (LT) are two well-known cases of sugar-binding proteins. The GM1:toxin complexes were chosen as test cases for the elaboration of a computational approach to the modeling of protein-saccharide interactions. The reliability of the method was evaluated on the LT:lactose complex. A model of this complex was built by performing a MC/EM conformational search of the sugar moiety within the binding pocket of LT, using the AMBER* force field and the GB/SA solvation model. The results are a reasonable reproduction of the reported X-ray structure of the complex. The same protocol was then applied to the LT:GM1 complex. The calculations were performed on a substructure that includes the protein shell within 5 A from GM1, three water molecules solvating Glu-51 carboxylate, and two water molecules at crystallographic sites 2 and 3. A satisfactory agreement was found with the recently published X-ray structure of the CT:GM1 complex. All the relevant interactions between the sugar and the residues involved in binding are well reproduced by the calculations. These results suggest that the substructure here identified can be taken as a realistic representation of the toxin binding surface and that the method presented in this paper can be used as a predictive tool in designing artificial LT (CT) binders and thus potential anticholera drugs.

Bacterial Toxins↗
PubMed1997

The histaminase activity of rat white adipocytes.

OBJECTIVE AND DESIGN: Investigate the reaction conditions which allow the measurement of high affinity histamine oxidation. MATERIAL: Isolated rat white adipocytes. METHODS: The histaminase activity of rat white adipocytes and its inhibition by B24 and MDL 72274 was measured fluorimetrically or radiochemically in different experimental conditions. RESULTS: Histamine oxidation by rat white adipocytes is enhanced by elevated pH and by the presence of bicarbonate ions. Under these conditions the oxidative deamination of histamine by white adipocytes, becomes comparable to that of other histaminases, suggesting that this amine oxidase activity may play a role in the catabolism of histamine in vivo. The specific semicarbazide-sensitive amine oxidase (SSAO) inhibitors MDL 72274 and B24 inhibit the oxidation of both histamine and benzylamine by the adipocyte preparation. CONCLUSIONS: Although there are kinetic differences between the behaviour of these two amine substrates, these results would be consistent with a SSAO being responsible for both activities.

Adipocytes↗
PubMed1997

Immunosuppressive activity of 13-cis-retinoic acid in rats: aspects of pharmacokinetics and pharmacodynamics.

Pharmacokinetics and pharmacodynamics of 13-cis-retinoic acid (13-cRA) administered at doses that suppress experimental autoimmune encephalomyelitis (EAE) have been investigated in rats. Serum concentration of the drug measured following oral administration of 37 mg/kg/12 h reached a peak of 1.8 x 10(-5) M in 2 h and linearly declined to 7.8 x 10(-7) M at hour 12. When spleen cells (SC) collected from 13-cRA-administered animals were cultured in vitro, their proliferative response to the T-cell mitogen concanavalin A (ConA) was suppressed and this effect was dependent on in vivo serum concentrations of the drug. In addition, in vitro exposure of antigen-specific T-cell lines to 13-cRA concentrations equivalent to those observed in vivo caused a dose-dependent suppression of the proliferation induced by the antigen as well as by T-cell mitogens. On a molar basis, 13-cRA showed a stronger in vitro immunosuppressive activity than two immunosuppressive agents used in human therapy, cyclosporin A and 6-mercaptopurin.

Animals↗
PubMed1997

Some histamine-related compounds interacting with the benzylamine-oxidizing activity of rat white adipocytes.

In rat white adipocytes histamine is oxidized by a semicarbazide-sensitive amine oxidase which has benzylamine or preferential substrate (Bz-SSAO). To determine whether Bz-SSAO could control the extracellular levels of histamine and other histamine-related compounds active in lipid mobilization, a series of histaminergic compounds was screened as possible substrates or inhibitors of Bz-SSAO activity. Histaminergic compounds with imidazolo or thiazolo groups are oxidized by rat white-adipocyte Bz-SSAO whereas S-isothiourea derivatives, with two- or three-carbon-atom alkyl chains between the isothiourea and the N,N-dimethyl residue are, instead, inhibitors of the enzyme. Amtamine has been identified as a selective, high affinity substrate for rat white adipocyte Bz-SSAO. This enzymatic degradation might represent a catabolic pathway for the drug. These results show that the histaminase property of the rat white-adipocyte enzyme Bz-SSAO also extends to other histamine derivatives active at histamine receptors.

Adipocytes↗
PubMed1996

Increased desensitization by picomolar phorbol ester of the endothelium-mediated effect of histamine in the perfused rat mesenteric bed.

The vasodilatatory, endothelium-mediated, effect of histamine (H), through H1 receptor, in the isolated and perfused mesenteric bed of the rat, undergoes strong desensitization during perfusion or repetitive injections of noradrenaline (NA) and H. The mesenteric bed completely desensitized to H is responsive to carbachol (C) and this latter compound does not affect the H desensitization. The homologous desensitization to C effect is very small, attaining less than 10% after 30 min of continuous perfusion. In this work the effect of inhibitors or activators of protein-kinase(s)-C (PKC) are studied during continuous perfusion of H or C in preparations preconstricted by NA. Staurosporine antagonizes the onset of the H desensitization, while the rate of desensitization in increased by phorbol-12-myristate-13-acetate (PMA). PMA, at a concentration from 10(-12) to 10(-10)M, selectively enhances the homologous desensitization of H, while at 10(-8)M it also produces a desensitization to C. At least two different PKC isoenzymes might be involved in the desensitization of the vasodilatatory effect of H and C in the isolated and perfused rat mesenteric bed.

Aging↗
PubMed1995

Semicarbazide-sensitive amine oxidase activity in white adipose tissue of the insulin-deficient rat.

We have investigated whether the effects in white adipose tissue due to insulin deficiency might also be related to an alteration of histamine levels which are regulated by semicarbazide-sensitive amine oxidase. The lack of circulating insulin induced by streptozotocin produced, in rat white adipose tissue, a loss of affinity of the semicarbazide-sensitive amine oxidase for histamine oxidation. In parallel, a decrease of cell transformation, measured by glycerol-3-phosphate dehydrogenase activity and an augmented sensitivity to histamine lipolysis were observed. These findings could contribute to the understanding of histamine metabolism and function in diabetic rats and to the knowledge concerning amine oxidases in this animal pathology.

Adipose Tissue↗
PubMed1994

Semicarbazide-sensitive amine oxidase activity of guinea pig dorsal skin.

A semicarbazide-sensitive amine oxidase activity with a high affinity for benzylamine (Bz.SSAO) (E.C. 1.4.3.6) is present in guinea pig dorsal skin. This enzymic activity oxidized benzylamine, histamine, 1,4-methylhistamine and acetylputrescine and was inhibited by semicarbazide and by B24 (3,5-diethoxy-4-aminomethylpyridine), a selective inhibitor of Bz.SSAO enzymes. It cross reacted with the antibodies raised against pure pig plasma benzylamine oxidase. Immunohistochemistry showed that it was localized in fibroblasts. Bz.SSAO activity of guinea pig dorsal skin increased during the process of skin healing. A treatment of the wounds with 3 micrograms of b-FGF significantly accelerated the process of skin healing and the increase of Bz.SSAO activity.

Amine Oxidase (Copper-Containing)↗
PubMed1994

Histaminase activity of mesenteric artery of the rat.

In rat mesenteric artery homogenates histamine is oxidatively deaminated at high rate whereas putrescine is a poor substrate. The oxidation of histamine appears to be mainly catalyzed by an SSAO enzyme with high affinity for benzylamine (Bz.SSAO). Histamine oxidation is inhibited by B24 (2,5-diethoxy-4-aminomethylpyridine), a selective inhibitor of Bz.SSAO enzymes, and reduced by the presence of benzylamine. The Bz.SSAO enzyme which is present in the rat mesenteric artery is not only able to oxidize histamine, but also methylamine, acetylputrescine and some methylated forms of histamine including 1,4-methylhistamine.

Amine Oxidase (Copper-Containing)↗
PubMed1994

The role of semicarbazide-sensitive amine oxidase with a high affinity for benzylamine (Bz. SSAO) in the catabolism of histamine in the mesenteric arterial bed of the rat.

In the mesenteric arterial bed of the rat the semicarbazide-sensitive amine oxidase with a high affinity for benzylamine (Bz. SSAO) (E.C. 1.4.3.6) is also able to oxidize histamine. In the perfused mesenteric arterial bed of the rat the complete inhibition of the Bz. SSAO obtained with a specific inhibitor, B24, almost completely reduces the efflux of imidazole acetic acid and increases the relaxing effect of histamine. Bz. SSAO appears to be the only enzyme present in these blood vessels able to catabolize histamine.

Amine Oxidase (Copper-Containing)↗
PubMed1993

Histamine lipolytic activity and semicarbazide-sensitive amine oxidase (SSAO) of rat white adipose tissue (WAT).

Histamine has previously been described as a possible substrate for the semicarbazide-sensitive amine oxidase activity (SSAO) of rat white adipose tissue (WAT). We report here on a histamine function in this tissue which concerns the activity of this deaminating system distinct from the classical diamine oxidase. Our results show that: (1) histamine plays a role in controlling rat adipose tissue lipolysis with the contribution of H1 and H2 receptors that participate in histamine lipolysis in an opposite way. Both H1 and H2 roles can be differentiated using selective agonists (2- and 4-methyl histamine) and antagonists (pyrilamine and cimetidine); (2) histamine might also control rat lipolysis induced by noradrenergic agonists; (3) the SSAO present in rat WAT controls histamine levels at the receptor sites as shown by the modification of histamine lipolytic potency obtained when inhibitors of this enzyme are used.

Adipose Tissue↗
PubMed1993

Metabolism of methylamine by semicarbazide-sensitive amine oxidase in white and brown adipose tissue of the rat.

The metabolism of [14C]methylamine (MA) by amine oxidase activity in rat white and brown adipose tissue homogenates, and in mature adipocytes from these tissues has been studied. Oxidation of MA was completely inhibited by 0.1-1 mM semicarbazide, without being affected by the monoamine oxidase (MAO) inhibitor, pargyline (1 mM), indicating that MA is metabolized by semicarbazide-sensitive amine oxidase (SSAO) and not by MAO. The mean Km for MA deamination in all of these sources was around 250-300 microM. SSAO activity towards MA was also demonstrated in white and brown pre-adipocytes, transformed to the adipose phenotype by treatment in culture for 7 days with lipogenic agents. These results are similar to previous findings that SSAO in vascular smooth muscle is able to metabolize aliphatic amines such as MA, and furthermore suggest that SSAO may play a role in adipose tissue function and/or maturation.

Adipose Tissue↗
PubMed1993

Some problems with the diamine oxidase (DAO) assay using putrescine as substrate in rat liver.

Determination of diamine oxidase (DAO) activity in rat liver preparations by measuring the formation of radioactive delta 1-pyrroline from 14C-putrescine is complicated by the complexity of competing metabolic pathways. This can lead to complete masking of the DAO activity present when rat liver homogenates are used as the enzyme source. However, subcellular fractionation of rat liver homogenates makes it possible to detect some putrescine oxidizing activity in the microsomal fraction when assayed at pH 8.5. When 1 mM putrescine was used as the substrate, over 90% of this activity was inhibited by 6 x 10(-4) M selegiline (deprenyl), indicating that monoamine oxidase (MAO) rather than DAO activity was being measured. The observed activity was also interfered with by agents that reduced acetylation processes and polyamine synthesis. A different picture appears when microM concentrations of putrescine are used: in these conditions all interference is strongly reduced and DAO activity can be measured in rat liver microsomes. Furthermore, kinetic studies on deaminative oxidation of 14C-putrescine at concentrations from 1 microM to 5 mM confirm the existence of two enzymes: one with a high affinity for the substrate and similar to intestinal mucosa DAO in its sensitivity to alpha-aminoguanidine, and the other one with a low affinity and selegiline-sensitive.

Amine Oxidase (Copper-Containing)↗
PubMed1993

Calcium modulatory properties of 2,6-dibutylbenzylamine (B25) in rat isolated vas deferens, cardiac and smooth muscle preparations.

1. In rat isolated vas deferens the new compound 2,6-dibutylbenzylamine (B25) evoked a series of repeating rhythmic contractions. Concentration-response curves constructed for this effect were bell-shaped, indicating a biphasic effect for this compound. By contrast, B25 depressed heart contractility without any visible positive inotropic or chronotropic activity. 2. Experiments with tetrodotoxin, reserpine, capsaicin, alpha-adrenoceptor blocking compounds and other agents permit us to exclude a release of neuromediators or a direct stimulation of post-synaptic receptors to account for the rhythmic effect of B25 in the rat vas deferens. 3. In the same tissue, the increase in 45Ca2+ uptake, the voltage-dependency as well as the dependence of the B25-induced rhythmic activity upon the external calcium concentration indicate a direct activation of voltage-sensitive calcium channels (VSCC). 4. Verapamil paradoxically stimulated the rhythmic effect of B25 in the rat vas deferens. La3+ was inactive while nifedipine was a weak inhibitor. By contrast Ni2+ and Mn2+ ions were good inhibitors (IC50 < 10(-4) M), suggesting that a possible opening of T-type VSCC underlies rhythmic effect of B25. 5. In radioligand binding studies competition experiments with [3H]-nitrendipine indicated that only at high concentrations was B25 able to interact with dihydropyridine-sensitive binding sites of heart and vas deferens smooth muscle. 6. B25 (3-30 microM) counteracted the inhibitory effects of omega-conotoxin GVIA in field-stimulated rat vas deferens.

Animals↗
PubMed1993

Skin wound healing: some biochemical parameters in guinea-pig.

Hairs were removed from the dorsal skin of guinea-pigs and 5-6 wounds (7 x 7 mm) were surgically induced by totally removing the epidermal and part of the dermal surface. They were then allowed to heal. The newly formed wound tissues were dissected at different times during the process and analysed by biochemical and histological methods. Hydroxyproline, proteins, DNA and semicarbazide-sensitive amine oxidase (SSAO) were measured, as were [14C]leucine and [3H]thymidine incorporation in some samples. The peroxidase-like activity of plasma albumin and the histology of wounds stained with haematoxylin-eosin were also studied. It was shown that SSAO enzymes, which are present in normal guinea-pig skin and have a high affinity for benzylamine are localized in fibroblasts. During skin healing in the newly formed tissue there was an increase in protein content which reached a maximum after 4-6 days; DNA content also increased. The rate of incorporation of [3H]thymidine and [14C]leucine paralleled DNA and protein content, respectively. The content of hydroxyproline had greatly decreased with respect to that in normal skin after 2-10 days. SSAO activity increased much less than DNA after 4 days whereas after 10-11 days it increased more than DNA, thus indicating that at this time it was probably produced by fibroblasts. No significant increase in the peroxidase-like activity of albumin was observed 4, 8 or 11 days after surgery. Treatment of the animals with methylprednisolone acetate (20 mg kg-1, i.m.) two days before surgery decreased the rate of skin healing but did not alter the level of albumin peroxidase activity of the plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Amine Oxidase (Copper-Containing)↗
PubMed1992

Histaminase activity in rat lung and its comparison with intestinal mucosal diamine oxidase.

In rat lung microsomes, an enzyme showing high histaminase activity is present. The oxidation of histamine is dependent on the presence of two enzymic activities, both inhibited by alpha-aminoguanidine and by B24, an inhibitor of semicarbazide-sensitive amine oxidases (SSAO) which have benzylamine as preferential substrate. These enzymic activities differ in substrate specificity: one appears to be a classical tissue bound SSAO enzyme with high affinity for benzylamine, the other a diamine oxidase (DAO) with properties that are very different from the classical DAO. This latter enzyme is not inhibition by high histamine concentrations and is more active at pH 8.5 than at pH 7.4.

Amine Oxidase (Copper-Containing)↗