Search PubMed⌕ Search

Biomedical subjects

P Valenti

Publications and source records attributed to P Valenti.

At least 19 recordsLinked to original sources
PubMed1998

Selective cardiodepressant activity of fluodipine, a fluorenone-1,4-dihydropyridine derivative.

The effect of the dihydropyridine derivative, 1,4-dihydro-2,6-dimethyl-4-(fluorenon-4-yl)pyridine-3,5-dicarboxyl ic acid diallyl ester (fluodipine) was studied in vitro in different rabbit, rat and guinea pig preparations and in vivo in the rabbit in order to characterize its pharmacological profile at cardiac and at vascular sites. Compared to nifedipine, fluodipine showed a similar cardiodepressant activity, and a much lower inhibitory activity on vascular contraction. The highest tissue selectivity was observed in guinea pig preparations: fluodipine was about 2-3 times more effective than nifedipine on chronotropism and inotropism in isolated atria, and about 150 times less effective on aortic strip contraction. Accordingly, fluodipine (i) showed high-affinity binding to guinea pig ventricular L-type cardiac Ca2+ channels (Ki=2.57 nM), (ii) was about 80 times less effective than nifedipine to inhibit Ca2+ influx in vascular smooth muscle cells and (iii) induced a significant reduction of heart rate in the anesthetized rabbit (ID25=8.5 mg kg(-1), i.v.) without affecting the blood pressure up to 20 mg kg(-1), whereas nifedipine showed a significant hypotensive effect at very low doses (ID25=0.18 mg kg(-1), i.v.). The pacemaker current If of rabbit sino-atrial node myocytes was not affected by fluodipine. These findings demonstrate that fluodipine exerts selective cardiodepressant activity, likely due to a higher affinity for cardiac than for vascular Ca2+ channels.

Anesthesia↗
PubMed1998

Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives.

Acetylcholinesterase (AChE) inhibitors are one of the most actively investigated classes of compounds in the search for an effective treatment of Alzheimer's disease. This work describes the synthesis, AChE inhibitory activity, and structure-activity relationships of some compounds related to a recently discovered series of AChE inhibitors: the omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxy xanthen-9-ones. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different parts of the parent molecule, and a theoretical model of the binding of one representative compound to the enzyme was developed. The biological properties of the series were investigated in some detail by considering not only the activity on isolated enzyme but the selectivity with respect to butyrylcholinesterase (BuChE) and the in vitro inhibitory activity on rat cerebral cortex as well. Some of the newly synthesized derivatives, when tested on isolated and/or AChE-enriched rat brain cortex fraction, displayed a selective inhibitory activity and were more active than physostigmine. In particular, compound 13, an azaxanthone derivative, displayed the best rat cortex AChE inhibition (190-fold higher than physostigmine), as well as a high degree of enzyme selectivity (over 60-fold more selective for AChE than for BuChE). When tested in the isolated enzyme, compound 13 was less active, suggesting some differences either in drug availability/biotransformation or in the inhibitor-sensitive residues of the enzyme when biologically positioned in rat brain membranes.

Acetylcholinesterase↗
PubMed1998

Overexpression of a hydrogen peroxide-resistant periplasmic Cu,Zn superoxide dismutase protects Escherichia coli from macrophage killing.

We have studied the effect of H2O2 on the activity of the Escherichia coli Cu,ZnSOD showing that, unlike the bovine enzyme, this bacterial Cu,ZnSOD is highly resistant to inactivation by hydrogen peroxide. In view of the key role played by oxygen radicals in bacterial killing by phagocytes, we have tested the ability of E. coli strains expressing different amounts of Cu,ZnSOD in the periplasmic space to survive the phagocytic attack of activated macrophages. Overexpression of the enzyme effectively protected the bacterial cell from macrophage killing. The results obtained support the hypothesis that in pathogenic bacteria periplasmic Cu,ZnSOD may reduce the oxyradical damages induced by the respiratory burst and therefore be important in virulence.

Animals↗
PubMed1998

Allylamine type xanthone antimycotics.

A number of xanthone derivatives bearing the basic chain of naftifine and butenafine antimycotics in 1, 2, 3, and 4 nuclear positions are described. The in vitro antifungal activity against representative strains of molds and yeasts is reported. Only butenafine xanthone analogues show significant activity against Cryptococcus neoformans, in particular the regioisomer 4d (1.5 micrograms/ml).

Allylamine↗
PubMed1998

Chemiluminescence imaging in bioanalysis.

The development, analytical performance and applications of chemiluminescence imaging as a tool for quantitative analyte localization in target biological specimens are described. The detection of acetylcholinesterase activity both in array format and on a target surface are described. A proposed application of the method is a 384 well microtiter format assay for high throughput screening of acetylcholinesterase inhibitors such as tacrine, a drug widely used in the treatment of Alzheimer's disease, and two recently developed analogues. The chemiluminescent system in conjunction with optical microscopy allowed localization of acetylcholinesterase in brain tissue sections. We also describe the chemiluminescent immunohistochemical localization of interleukin 8 in Helicobacter pylori infected gastric mucosa cryosections and an in situ hybridization assay for the detection of herpes simplex virus DNA in single cells.

Acetylcholinesterase↗
PubMed1998

Coumarin 1,4-dihydropyridine derivatives.

A series of 1,4-dihydropyridines bearing a coumarin moiety in 4-position was synthesized. The compounds were evaluated for inotropic, chronotropic and calcium antagonist activities. The replacement of the o-nitrophenyl moiety of nifedipine with a coumarin or phenylcoumarin system is accompanied by a decrease of the activity on myocardial and vascular parameters, but the synthesized compounds showed selective inhibiting effects on cardiac contractility and frequency.

Animals↗
PubMed1998

Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection.

Lactoferrin is a mammalian iron-binding glycoprotein present in many biological secretions, such as milk, tears, semen and plasma and a major component of the specific granules of polymorphonuclear leucocytes. The effect of bovine lactoferrin (BLf) in apo-form or saturated with ferric, manganese or zinc ions, on human immunodeficiency virus type 1 (HIV-1) infection in the C8166 T-cell line was studied. Both HIV-1 replication and syncytium formation were efficiently inhibited, in a dose-dependent manner, by lactoferrins. BLf in apo and saturated forms markedly inhibited HIV-1 replication when added prior to HIV infection or during the virus adsorption step, thus suggesting a mechanism of action on the HIV binding to or entry into C8166 cells. Likewise, the addition of Fe3+BLf prior to HIV infection and during the attachment step resulted in a marked reduction of the HIV-1 DNA in C8166 cells 20 h after infection. The potent antiviral effect and the high selectivity index exhibited by BLf suggest for this protein, in apo or saturated forms, an important role in inhibiting the early HIV-cell interaction, even though a post adsorption effect cannot be ruled out.

Adsorption↗
PubMed1998

Metal complexes of bovine lactoferrin inhibit in vitro replication of herpes simplex virus type 1 and 2.

The inhibitory effect of bovine lactoferrin (BLf) saturated with ferric, manganese or zinc ions, on the infection of Vero cells by human herpes simplex virus type 1 (HSV1) and 2 (HSV2) was investigated. Viral infectivity determined by intracellular antigen synthesis and plaque formation was efficiently inhibited by metal saturated lactoferrins in a dose-dependent manner. Effective BLf concentrations which reduced the infection by 50% ranged from 5.2 to 31 micrograms ml-1 and were far below the cytotoxicity threshold. Fe3+BLf and Mn2+BLf exhibited selectivity indexes higher than Zn2+BLf and apoBLf for both viruses and the effect was mainly directed towards the early steps of infection. The slight viral inhibition shown by the citrate complexes of the different metals could indicate that the antiviral effect was not significantly influenced by Fe3+, Mn2+ or Zn2+ ions delivered by BLf into the cells.

Animals↗
PubMed1998

Natural milk fatty acids affect survival and invasiveness of Listeria monocytogenes.

The effects of 12 fatty acids, naturally occurring in milk from several mammalian species, on the survival and invasion ability of Listeria monocytogenes, a food-borne pathogen, were determined. The survival was tested in the presence of 200 micrograms ml-1 fatty acids suspended in brain hearth infusion broth or in storage conditioning solution (NaCl 1%) of Mozzarella cheese, an Italian soft unripened cheese, at pH 7.0 or 5.0. Lauric (C12:0), linoleic (C18:2) and linolenic (C18:3) acids exerted the strongest bactericidal activity. The invasive efficiency of L. monocytogenes, determined in the Caco-2 enterocyte-like cell line, was strongly decreased in the presence of the fatty acids tested (from about 20 to 500-fold). This research suggests that naturally occurring fatty acids of milk, supplemented in milk derivatives, could affect both bacterial growth and invasiveness and consequently, could serve as barriers towards L. monocytogenes infection.

Animals↗
PubMed1998

[Colposuspension with propylene mesh. A new technique for correction of urinary stress incontinence].

The results of colposuspension for correcting urinary stress incontinence, both transabdominal, like Burch procedure, and transvaginal like Stamey-Pereyra procedure are, up to date, good, but not perfect at long-term. The cutting of the tissues from distal end of the sutures seems to be the main reason of failure of the operation. The authors propose a new technique of colposuspension by means of a particular suture made by the joining a prolene-mesh and a prolene-suture bilaterally placed along the urethra to obtain a strong, but natural support without risk of urethral erosion. The authors present the preliminary report of the first sixteen consecutive operations performed in patients with genuine urinary stress incontinence of first and second degree, according to Blaivas classification, diagnosed by medical history, objective findings, urodynamic tests and cystography. The follow-up in all the patients was six months: undoubtedly brief, but sufficient to refer on the feasibility and the efficacy of the procedure, the easy performing and the scarce onset of early complications as wound infection or troubles related to the prolene-mesh.

Adult↗
PubMed1997

A novel non-heme iron-binding ferritin related to the DNA-binding proteins of the Dps family in Listeria innocua.

A multimeric protein that behaves functionally as an authentic ferritin has been isolated from the Gram-positive bacterium Listeria innocua. The purified protein has a molecular mass of about 240,000 Da and is composed of a single type of subunit (18,000 Da). L. innocua ferritin is able to oxidize and sequester about 500 iron atoms inside the protein cage. The primary structure reveals a high similarity to the DNA-binding proteins designated Dps. Among the proven ferritins, the most similar sequences are those of mammalian L chains that appear to share with L. innocua ferritin the negatively charged amino acids corresponding to the iron nucleation site. In L. innocua ferritin, an additional aspartyl residue may provide a strong complexing capacity that renders the iron oxidation and incorporation processes extremely efficient. This study provides the first experimental evidence for the existence of a non-heme bacterial ferritin that is related to Dps proteins, a finding that lends support to the recent suggestion of a common evolutionary origin of these two protein families.

Amino Acid Sequence↗
PubMed1997

Synthesis and bone resorption effect of alkoxy-substituted xanthones.

A topological modification of ipriflavone 1, a recent antiosteoporotic drug, is described. The flavone moiety of 1 has been replaced by a xanthone one. Among the new derivatives, the 3,6-diisopropoxyxanthone (2a) has shown significant bone resorption inhibition in in vitro and in vivo tests.

Animals↗
PubMed1997

Antirotaviral activity of milk proteins: lactoferrin prevents rotavirus infection in the enterocyte-like cell line HT-29.

Different milk proteins were analyzed for their inhibitory effect on either rotavirus-mediated agglutination of human erythrocytes or rotavirus infection of the human enterocyte-like cell line HT-29. Proteins investigated were alpha-lactalbumin, beta-lactoglobulin, apo-lactoferrin, and Fe(3+)-lactoferrin, and their antiviral action was compared with the activity of mucin, a milk glycoprotein known to affect rotavirus infection. Results obtained demonstrated that beta-lactoglobulin, apo- and Fe(3+)-lactoferrin are able to inhibit the replication of rotavirus in a dose-dependent manner, apo-lactoferrin being the most active. It was shown that apo-lactoferrin hinders virus attachment to cell receptors since it is able to bind the viral particles and to prevent both rotavirus haemagglutination and viral binding to susceptible cells. Moreover, this protein markedly inhibited rotavirus antigen synthesis and yield in HT-29 cells when added during the viral adsorption step or when it was present in the first hours of infection, suggesting that this protein interferes with the early phases of rotavirus infection.

Animals↗
PubMed1997

Very distal finger amputations: replantation or "reposition-flap" repair?

Management of very distal finger amputations is still controversial. Successful replantation results in an almost normal finger but is not without problems, such as technical difficulty, risk of failure and cost. "Reposition-flap" repair is a simpler procedure: it consists of distal bone and nail bed "graft-reposition" and pulp reconstruction by a flap. We compare ten successful replantations and six reposition-flap reconstructions. Replantation has several advantages over reposition-flap repair in terms of less finger shortening, longitudinal nail curvature, absence of PIP flexion contracture and shorter time off work. The results of reposition-flap repair are less satisfactory, but it is nevertheless a useful alternative when replantation is impossible or has failed.

Adolescent↗
PubMed1997

Synthesis of a series of Homopterocarpane derivatives with potential antitumor and anti-AIDS activity.

The synthesis of a series of derivatives related to (+/-) cis 6a, 12a-dihydro-6H,7H-[1]-benzopyrano-[4,3-b]-[1]-benzopyran (Homopterocarpane) is described. The synthesized derivatives have been tested at National Cancer Institute in its in vitro anti-cancer and anti-AIDS screening programs. The synthesized compounds are inactive in anti-HIV assay, while some show a GI50 < 100 microM (and < 50 microM in several cell lines) in NCI antitumor screening.

Anti-HIV Agents↗
PubMed1997

Modulation of pharmacological profile of diphenylethane (lefetamine-type) derivatives.

With the aim to split the pharmacological properties of lefetamine (CAS 14148-99-3), some structural modifications of this compound have been studied. The basic group of lefetamine has been shifted from the alkyl chain to the vicinal phenyl ring and the N-substitution has been changed. The dimethylaminomethyl derivatives and chiefly the o-morpholinometyhl exhibited a strong anti-visceral chemical antinociception activity stripped of thermal antinociception properties and physical dependence liability. Furthermore, through the introduction of a diethylaminomethyl group in the lefetamine structure some derivatives were selected exhibiting besided a significant increase in the anti-visceral chemical antinociception activity, remarkable local anesthetic properties.

Analgesics, Non-Narcotic↗