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Biomedical subjects

C Conti

Publications and source records attributed to C Conti.

At least 55 records · Page 3Linked to original sources
PubMed1993

Inhibition of Sindbis virus replication by cyclopentenone prostaglandins: a cell-mediated event associated with heat-shock protein synthesis.

Cyclopentenone prostaglandins (PGs) have been shown to inhibit the replication of several DNA and RNA viruses. Here we report on the effect of prostaglandin A1 (PGA1) on the multiplication of a positive strand RNA virus, Sindbis virus, in Vero cells under one-step multiplication conditions. PGA1 was found to inhibit Sindbis virus production dose-dependently, and virus yield was reduced by more than 90% at the concentration of 8 micrograms/ml, which was non-toxic to the cells and did not inhibit DNA, RNA or protein synthesis in Vero cells. The cyclopentenone prostaglandin delta 12-PGJ2 was also shown to be a potent inhibitor of Sindbis virus replication. Virus-induced reduction of [3H]uridine uptake by cells was partially prevented by PGA1 treatment, which also caused a 1 h delay in the peak of virus RNA synthesis. SDS-PAGE analysis of [35S]methionine-labeled proteins showed that PGA1 moderately inhibited the synthesis of the viral structural proteins E1, E2 and C, and induced the synthesis of a 72 kDa M(r) protein, identified as a heat-shock protein related to the HSP70 group, in both virus-infected and uninfected cells. Actinomycin D treatment completely prevented PGA1-antiviral activity, indicating that a cellular product is responsible for this action. PGA1-induced HSP70 is a good candidate for this role.

Animals↗
PubMed1992

Constituents of Eriobotrya japonica. A study of their antiviral properties.

The CHCl3 extract of Eriobotrya japonica from an Italian source was shown to contain four new triterpene esters, namely, 23-trans-p-coumaroyltormentic acid [1], 23-cis-p-coumaroyltormentic acid [2], 3-O-trans-caffeoyltormentic acid [3], and 3-O-trans-p-coumaroylrotundic acid [4], in addition to three common ursolic acid derivatives 5, 6, and 7. An investigation of the antiviral properties of compounds 1-7 revealed that only 3 significantly reduced rhinovirus infection. The compounds were ineffective towards human immunodeficiency virus type 1 (HIV-1) and Sindbis virus replication.

Antiviral Agents↗
PubMed1992

Mechanism of action of the antirhinovirus flavanoid 4',6-dicyanoflavan.

4',6-Dicyanoflavan (DCF), a new antirhinovirus compound, was shown to inhibit an early event of rhinovirus type 1B replication in HeLa cells. When DCF was present from the beginning of infection or was added no later than the first hour of infection, the compound completely prevented viral RNA and protein synthesis and the virus-induced shutoff of host translation. DCF had no adverse effect either on virus binding to the cell membrane or on virus penetration into cells, whereas it delayed the uncoating kinetics of neutral redencapsidated rhinovirus. DCF also prevented mild acid or thermal inactivation of virus infectivity, although it reversibly interacted with virions. These results suggest that the stabilizing effect of DCF on virion capsid conformation is responsible for uncoating inhibition.

Antiviral Agents↗
PubMed1992

Comparative effect of galanin and pyridostigmine on the growth hormone response to growth hormone-releasing hormone in normal aged subjects.

The aim of our study was to investigate the effects of aging on the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) alone and in combination with either the neuropeptide galanin or the acetylcholinesterase inhibitor pyridostigmine (PD) in normal subjects. In protocol 1 (GHRH/galanin), 9 old healthy volunteers, ranging in age from 68 to 97 years, and 6 young subjects, ranging in age from 25 to 31 years, received: (a) human GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) porcine galanin, 500 micrograms in 100 ml saline, as an intravenous infusion from -10 to 30 min combined with GHRH, 100 micrograms i.v. at time 0. In protocol 2 (GHRH/PD), 14 old healthy volunteers, ranging in age from 65 to 91 years, and 11 young subjects, ranging in age from 19 to 34 years, received: (a) GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) PD, 120 mg administered per os 60 min before GHRH, 100 micrograms as an intravenous bolus. Blood samples for GH were drawn at -75, -60 (time of PD administration), -45, -30, -15, -10 (time of beginning of galanin infusion), 0 (time of GHRH injection), 15, 30, 45, 60, 90, and 120 min. The GH response to GHRH was significantly (< 0.05) enhanced either by galanin or PD pretreatment both in young and old subjects. However, the GH response to GHRH alone or combined with either galanin or PD was significantly greater in the young subjects as compared to the old subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The Elmslie-Trillat procedure for recurrent subluxation of the patella. One to five year follow-up.

Thirty-four patients who had undergone the Elmslie-Trillat procedure from 1985 to 1989 were examined in order to evaluate the effectiveness of this operation in the treatment of recurrent subluxation of the patella. The result of an increased Q angle accompanied by patella alta, femoral sulcus dysplasia, or vastus medialus obliquus dysplasia was also studied. Only those patients with recurrent subluxation of the patella took part in this study; cases of habitual or permanent dislocation, potential instability, traumatic dislocation, and degenerative arthritis were excluded. The patients were reviewed both clinically and radiographically, and the A.R.P.E.G.E. scoring system was used to evaluate the results. The follow-up period ranged from 1 year to 5 years and 4 months, with an average of 3 years. The overall results were excellent or good in 77% of the cases, as was the subjective knee stability rating in 87% of the cases and the pain rating in 82% of the cases. Recurrence of the subluxation was observed in only one instance. The results were not significantly different when the groups of patients with patella alta and type 1 femoral sulcus dysplasia were considered separately. The results were also excellent in the patients who underwent the Elmslie-Trillat procedure with reconstruction of the vastus medialis obliquus. In conclusion, surgical realignment of the anterior tibial tubercle confirmed its reliability in the treatment of recurrent subluxation of the patella. In cases of patella alta, the authors recommend lowering the anterior tibial tubercle only when the Insall-Burstein index is greater than 1.3. Femoral sulcus-plasty should be performed in cases of type 3 sulcus dysplasia.

Adolescent↗
PubMed1992

Effect of electric charged molecules on Sindbis virus hemagglutination and hemolysis.

The role of electrostatic interactions in the attachment and fusion at acidic pH of Sindbis virus (SNV) with goose erythrocytes was studied, investigating the effect of several anionic and cationic polyelectrolytes on SNV hemagglutination and hemolysis. In order to establish the target of active drugs, the compounds were incubated either with the virus particles or with the erythrocytes. Dextran sulfate was the only compound able to inhibit the attachment of SNV to the erythrocytes. Fusion of virus with red cells was reduced dose-dependently by the polyanions dextran sulfate, mucin and polygalacturonic acid. On the contrary two polycations, polylysine and polybrene, enhanced viral hemolytic activity. However the effect of polyions is not exclusively related to the electric charge since ineffective molecules were found in both classes of compounds.

Animals↗
PubMed1991

Effect of polyions on the early events of Sindbis virus infection of Vero cells.

To clarify the role of electrostatic interactions in the binding of Sindbis virus (SNV) to cell membrane receptors, we investigated the effect of different polyions on the initial steps of infection of Vero cells by the virus. Several polyanions (mucin, heparin, polygalacturonic acid) and polycations (polylysine, protamine, polybrene) were able to reduce the replication of SNV when present in the viral adsorption period, whereas others (chondroitin sulfate, polymyxin B sulfate, histone) were devoid of any activity. Therefore the electric charge alone is not sufficient to explain the action of compounds. The effects of polyions on receptor binding, on bound virus, and on internalized virus have been examined. All the drugs inhibited SNV infection by affecting its binding to the cellular receptor. The results indicated that heparin and mucin act directly on the virus particle while polycations bind to the cell membrane receptor for the virus, protamine being effective on both targets. Since among polyanions glycosaminoglycans showed a strong inhibiting activity, the involvement of these molecules in the virus surface receptor was assessed by enzyme digestion of cell membrane with heparinase and chondroitin ABC lyase.

Animals↗
PubMed1991

Role of membrane phospholipids and glycolipids in cell-to-cell fusion by VSV.

To identify membrane components of CER cells interacting with vesicular stomatitis virus (VSV) during fusion at acidic pH (fusion from without, FFWO) two different approaches have been used, i.e. (i) treating the whole cells with enzymes and (ii) testing the ability of isolated membrane molecules to interfere with FFWO. Phospholipase A2 and C digestion of cells greatly reduced syncytia formation, pointing towards the involvement of lipid structures as target sites for VSV. Cell susceptibility to FFWO was also reduced after neuraminidase, beta-galactosidase or periodate treatment, suggesting that carbohydrate residues may participate in a complex receptor structure required for virus fusion. When membrane molecules were examined separately for their ability to inhibit viral FFWO, phosphatidylserine, phosphatidylinositol, sphingomyelin, cholesterol and GM3 ganglioside were found to be active, confirming the role of membrane lipid moiety in the cell surface structures involved in the early phases of VSV infection.

Cell Fusion↗
PubMed1991

Enantiomeric separation of substituted flavanoids by LC-DAD.

A variety of racemic flavanoids with anti-rhinovirus activity have been resolved for the first time by HPLC, using a chiral stationary phase. Baseline separation was easily obtained for racemic 4',6-dichloroisoflavan (V). The absolute configurations of two enantiomers (Va and Vb) were established by comparing their circular dichroism curves with those of other known isoflavans. Both the isomers were tested against human rhinovirus serotype 1B infection in vitro; the S form was approximately four times more effective than the R form.

Antiviral Agents↗
PubMed1991

Structure and in vitro antiviral activity of triterpenoid saponins from Calendula arvensis.

A reinvestigation of the aerial parts of Calendula arvensis afforded, in addition to the oleanolic acid glycosides 1-4 (4), the new glycoside 5 whose structure was elucidated by spectral and chemical studies and determined as 3-O-(beta-D-galactopyranosyl-(1----3) [beta-D-glucopyranosyl-(1----4)]-beta-D-glucopyranosyl) oleanolic acid (28----1)-beta-D-glucopyranosyl ester. Furthermore, some antiviral tests were performed on glycosides 1-5 and on 5a, the hydrolysis product of 5, towards vesicular stomatitis virus (VSV) and rhinovirus (HRV) infection in cell cultures. An inhibitory effect against VSV multiplication was observed for all the compounds tested while HRV replication was significantly affected only by compound 3.

Animals↗
PubMed1991

Antiviral activity of constituents of Tamus communis.

The antiviral activity of the phenanthrene derivatives 1-6, of the spyrostane triglycosides dioscin (7) and gracillin (8), of the furostanol tetraglycosides methylprotodioscin (9), its (25S) epimer methylprotoneodioscin (10), and methylprotogracillin 11, have been tested towards two RNA viruses: vesicular stomatitis virus and human rhinovirus type 1B. All these products were extracted from the rizomes of Tamus communis L; compound 11 was isolated also from Asparagus cochinchinesis, together with pseudoprotodioscin (12), a 20 (22)-unsaturated furostanoside, which was also investigated for antiviral activity. The results were of some interest mainly for the phenanthrene derivatives.

Animals↗
PubMed1991

Induction of short-term markers of tumor promotion by organic peroxides.

Experiments from different laboratories have shown that benzoyl peroxide (BzPo) and other organic peroxides are effective tumor promoters in the mouse skin two-stage carcinogenesis system. In the present paper we have studied the short-term effect of six other organic peroxides, which have not been previously assayed as skin tumor promoters. These compounds were chosen for their molecular diversity, the type of radical predicted to be formed, solubility and availability. The parameters evaluated in this study include a series of short-term markers of tumor promotion, hyperplasia, induction of dark basal keratinocytes and induction of ornithine decarboxylase activity. After single applications the biological activity of the compounds was: m-chloroperoxybenzoic acid greater than di-m-methylbenzoyl peroxide greater than dicumyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)mono-peroxycarbonate greater than benzoyl peroxide greater than di-m-chlorobenzoyl peroxide greater than di-t-butyl peroxide greater than t-butyl hydroperoxide. After multiple applications, the order of activity of the compounds was: dicumyl peroxide greater than di-m-methyl-benzoyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)monoperoxy carbonate greater than m-chloroperoxybenzoic acid greater than di-m-chlorobenzoyl peroxide greater than t-butyl hydroperoxide greater than benzoyl peroxide greater than di-t-butyl peroxide. The difference of activity among the different compounds did not seem to correlate directly with the chemical stability of the compound; it is more likely that the activity depends on different factors such as percutaneous absorption, metabolism, and the rate of free radical formation in vivo. The data presented here further support the association between free radicals and tumor promotion since all of the compounds, with the exception of one, were active in inducing the short-term markers of tumor promotion. It will also establish conditions for future tumor experiments.

Animals↗
PubMed1991

Virulence plasmids of enteroinvasive Escherichia coli and Shigella flexneri integrate into a specific site on the host chromosome: integration greatly reduces expression of plasmid-carried virulence genes.

The ability of enteroinvasive Escherichia coli and Shigella flexneri to cause disease depends on the presence of a large virulence plasmid (pINV). In this report we show that pHN280, the pINV of the O135:K-:H- enteroivasive strain E. coli HN280, and pWR100, the pINV of S. flexneri serotype 5 strain M90T, are able to integrate into a specific site on the host chromosome. pINV-integrated HN280 and M90T strains required methionine (Met-) to grow in minimal medium, were noninvasive, did not produce contact-mediated hemolysin, and had lost the ability to bind Congo red (Crb-) at 37 degrees C. Immunoblots of whole bacterial extracts from pHN280-integrated HN280 derivatives revealed that integration severely reduced the expression of ipa and virG (icsA) plasmid genes. Met- HN280 and M90T derivative strains spontaneously generated Met+ revertants that either contained excised forms of pINV or had lost pINV. Restriction analysis of excised pINVs showed that they either were virtually identical to parental pINVs (precise excision) or had suffered some deletion (imprecise excision). Precisely excised pINVs expressed the full pattern of virulence, whereas imprecisely excised pINVs were always Crb- and noninvasive. The revertion to Met+ was shown to be recA dependent, indicating that homologous plasmid and chromosomal DNA sequences are involved in the integration-excision process. The maintainance of pINV through integration and downregulation of its virulence genes may represent an advantageous mechanism for enteroinvasive bacteria, particularly when they are outside host cells and/or have to face adverse environmental conditions.

Animals↗
PubMed1990

Effect of inhibitors of cytoplasmic structures and functions on rabies virus infection in vitro.

The effect in vitro of some cytoplasmic structure and function inhibitors on the different stages of rabies virus infection was investigated. Treatment of fibroblasts (CER) and human neuroblastoma cells (IMR-32) with substances acting on low pH intracellular compartments (methylamine and monensin) prevented rabies virus genome delivery in the cytosol. An early inhibition of viral infection was also obtained in the presence of B and D cytochalasins and trifluoperazine which interact with microfilament structures. Treatment with colchicine and vinblastine did not affect rabies multiplication, suggesting that microtubules are not involved in this process. However, the multiplication of prebound virions did not take place in the presence of inhibitors of oxidative phosphorylation (sodium azide and CCCP) and of glycolysis (2-deoxy-D-glucose) indicating that rabies virus replication is largely energy-dependent in both host cells examined.

Animals↗
PubMed1990

Activities and mechanisms of action of halogen-substituted flavanoids against poliovirus type 2 infection in vitro.

The effects of some halogen-substituted flavanoids (dichloroflavan, halogenated isoflavans, and isoflavenes) on poliovirus type 2 infection was examined. Only two isoflavenes exhibited a significant inhibitory activity on the virus-induced cytopathic effect and plaque formation. In a single cycle of viral replication, both compounds reduced the viral yield by approximately 90%. The presence of the isoflavenes from the beginning of infection or during the adsorption period only prevented the shutoff of host translation and viral RNA and protein synthesis, suggesting that the drugs blocked an early step of viral replication. Indeed, both isoflavenes were not virucidal, did not protect virus infectivity from heat inactivation, and had no measurable effect on the binding of virus to cells, viral penetration, and uncoating of the viral RNA. In contrast, both compounds significantly reduced the infectivity of free viral RNA. The possibility that compounds interfere with poliovirus replication at a very early stage of translation of the input RNA is discussed.

Flavonoids↗
PubMed1990

Effect of desferrioxamine B, a metal chelating agent, on rhabdovirus multiplication.

It has been suggested that the antiviral activity shown by chelating agents towards different viruses is probably related to the action on viral nucleic acid polymerases which require metal ions as essential cofactors. Desferrioxamine B, a metabolite from Streptomyces pilosus which chelates ions (Fe3+, Al3+, Cu2+, Zn2+, Co2+) from intracellular and external compartments, has been tested for its activity on the multiplication of VSV and rabies virus in CER cells. While desferrioxamine B was ineffective on rabies virus multiplication, it was shown to reduce plaque formation, cytopathic effect and viral yield by VSV at both low and high multiplicity of infection. The activity of the drug was not due to a direct action on virions outside the cells, but was probably related to an alteration in the delicate balance of intracellular ions which could in turn be critical for VSV multiplication.

Animals↗
PubMed1989

Blunt injuries to the aortic arch vessels.

Thirty patients with 33 vascular injuries from blunt trauma to the brachiocephalic branches of the aortic arch are reported. To our knowledge, this is the largest series reported to date of blunt injuries to these vessels. Mechanisms of injury included deceleration, traction, and crush. Half of the injured vessels were the innominate artery, and a quarter each were the common carotid and subclavian arteries. Common associated injuries were head injuries, hemopneumothorax, lung contusion, long bone fractures, and brachioplexus injuries. Widened mediastinum and extrapleural hematoma were common radiographic findings, and aortic rupture was frequently suspected. Angiography was performed in all patients to identify precisely the nature and site of the injury. Surgical approaches varied with the anatomical site of the injury and required consideration of vascular control in chest, neck, and upper extremity. Twenty-seven patients are alive 6 months to 10 years after injury. Eighteen of 20 vascular reconstructions were patent at follow-up. No patient with brachioplexus injury had return of neurological function.

Adolescent↗