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1.
Acta Virol ; 61(3): 341-346, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28854799

RESUMEN

Activity of three photosensitizing phthalocyanine derivatives was tested for photodynamic inactivation towards two coated and two non-enveloped viruses - bovine viral diarrhea virus (BVDV), influenza virus A(H3N2), poliovirus type 1 (PV-1) and human adenovirus type 5 (HAdV5). In the case of coated viruses, a combination of virucidal and irradiation effects was registered by octa-methylpyridyloxy-substituted Ga phthalocyanine (Ga8) toward BVDV, whereas tetra-methylpyridyloxy-substituted Ga phthalocyanine (Ga4) revealed a marked photoinactivation only. No such effect was observed towards influenza A virus. In contrast, the photoinactivating potential of Ga4 and Ga8 marked very high values on naked viruses, especially on HAdV5, at which both the virucidal as well as the irradiation effects became combined.


Asunto(s)
Adenovirus Humanos/efectos de los fármacos , Virus de la Diarrea Viral Bovina/efectos de los fármacos , Indoles/farmacología , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Poliovirus/efectos de los fármacos , Animales , Bovinos , Línea Celular , Perros , Humanos , Isoindoles , Células de Riñón Canino Madin Darby
2.
Drug Res (Stuttg) ; 66(12): 639-643, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27552486

RESUMEN

Anti-enteroviral chemotherapeutics for clinical use are not registered so far, mainly due to the rapid development of drug-resistance. One of the possible approaches to overcome this problem is the use of combined chemotherapy. However, its application consisting of simultaneously given drugs, is not efficacious because of the development of multiple resistance. Here we present a novel approach for combined application of anti-enteroviral compounds, consisting of a consecutive alternating administration (CAA) course. CAA was tested on 2 in vivo models of Coxsackievirus B3 infection in newborn mice at inoculation dose of 20 MLD50 (50% mouse lethal dose): neurotropic (Nancy strain) and cardiotropic (Woodruff strain) infections. Compounds partnering in a triple combination were selected as enterovirus (EV) replication inhibitors with different mode of action - disoxaril (a VP1 blocker), guanidine.HCl (targeting 2C protein) and oxoglaucine (attacking 3A coding region). The application of this combination by CAA course resulted in around 40 and 60% survival rate in mice infected with Nancy and Woodruff virus, respectively, accompanied by a marked lengthening of the mean survival time (MST). The results obtained are proofs for the prospect of the treatment course by a triple combination through the CAA scheme as an approach interfering the occurrence of drug resistance at EV infections.


Asunto(s)
Antivirales/administración & dosificación , Infecciones por Coxsackievirus/tratamiento farmacológico , Enterovirus Humano B/efectos de los fármacos , Animales , Animales Recién Nacidos , Apomorfina/administración & dosificación , Apomorfina/análogos & derivados , Quimioterapia Combinada/métodos , Guanidina/administración & dosificación , Isoxazoles/administración & dosificación , Ratones , Ratones Endogámicos ICR
3.
Hum Biol ; 87(1): 19-28, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26416319

RESUMEN

Ancient (proto-) Bulgarians have long been thought of as a Turkic population. However, evidence found in the past three decades shows that this is not the case. Until now, this evidence has not included ancient mitochondrial DNA (mtDNA) analysis. To fill this void, we collected human remains from the 8th to the 10th century AD located in three necropolises in Bulgaria: Nojarevo (Silistra region) and Monastery of Mostich (Shumen region), both in northeastern Bulgaria, and Tuhovishte (Satovcha region) in southwestern Bulgaria. The phylogenetic analysis of 13 ancient DNA samples (extracted from teeth) identified 12 independent haplotypes, which we further classified into mtDNA haplogroups found in present-day European and western Eurasian populations. Our results suggest a western Eurasian matrilineal origin for proto-Bulgarians, as well as a genetic similarity between proto- and modern Bulgarians. Our future work will provide additional data that will further clarify proto-Bulgarian origins, thereby adding new clues to the current understanding of European genetic evolution.


Asunto(s)
ADN Mitocondrial/historia , Etnicidad/genética , Evolución Molecular , Población Blanca/genética , Bulgaria/etnología , Historia Medieval , Humanos
4.
Artículo en Inglés | MEDLINE | ID: mdl-27442376

RESUMEN

BEN is a primary, chronic tubulointerstitial nephritis characterized with chronic anemia, absence of edema, xantoderma, normal blood pressure and normal findings on the fundus oculi. The disease is distributed in restricted areas in Bulgaria, Romania, Croatia, Bosnia, Former Yugoslavia. Despite numerous studies on genetic and environmental factors and their possible involvement in BEN, its etiopathogenesis still remains elusive. Our recent study aim to elucidate the possible epigenetic component in BEN development. Whole genome DNA array methylation analysis was applied to compare the methylation profiles of male and female BEN patients from endemic regions in Bulgaria and Serbia and healthy controls. All three most prominent candidate genes with aberrations in the epigenetic profile discovered with this study are involved in the inflammatory/immune processes and oncogenesis. These data are in concordance with the reported pathological alterations in BEN. This research supports the role of epigenetic changes in BEN pathology. Exome sequencing of 22.000 genes with Illumina Nextera Exome Enrichment Kit revealed three mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients which encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.


Asunto(s)
Nefropatía de los Balcanes/genética , Metilación de ADN , Epigénesis Genética , Epigenómica , Genoma Humano , Genómica , Nefropatía de los Balcanes/diagnóstico , Nefropatía de los Balcanes/epidemiología , Bulgaria/epidemiología , Estudios de Casos y Controles , Análisis Mutacional de ADN , Epigenómica/métodos , Exoma , Femenino , Perfilación de la Expresión Génica , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genómica/métodos , Proteoglicanos de Heparán Sulfato/genética , Humanos , Masculino , Mutación , Elastasa Pancreática/genética , Fenotipo , Canales de Potasio de Dominio Poro en Tándem/genética , Factores de Riesgo , Serbia/epidemiología
5.
Antiviral Res ; 110: 104-14, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25111906

RESUMEN

The plant-derived polyphenolic compounds castalagin, vescalagin and grandinin (C-glucosidic ellagitannins containing nonahydroxyterphenoyl) manifested a strong inhibitory effect on the replication of acyclovir-resistant strains of herpes simplex viruses (HSV) type 1 and 2 in MDBK cells in focus forming units (i.e., microscopically registered microplaques) reduction assay and in two variants of cytopathic effect inhibition test. The effect on the acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) strain was markedly higher compared to that on the ACV-resistant herpes simplex virus type 2 (HSV-2). The three compounds showed comparable levels of antiviral activity against ACV-resistant HSV strains, in contrast with previous results where castalagin exerted the highest degree of activity against wild type HSV strains (Vilhelmova et al., 2011). Combinations of ellagitannins and ACV were tested on the ACV-resistant strains of both HSV-1 and 2 and produced synergistic effects that were revealed by applying the three-dimensional approach of Prichard and Shipman (1990). The ellagitannin(s)-ACV combination applied against ACV-resistant HSV-1 produced a much stronger synergistic effect compared to the effect observed against ACV-resistant HSV-2. The study of the effects of the combination ellagitannin(s)-ACF on intact cell monolayers did not show any toxicity resulting from interaction between the two substances. Altogether, the results obtained in this study demonstrate the highly promising potential of these plant polyphenols as antiherpetic agents.


Asunto(s)
Aciclovir/farmacología , Glicósidos/farmacología , Herpesvirus Humano 1/crecimiento & desarrollo , Herpesvirus Humano 2/crecimiento & desarrollo , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Taninos Hidrolizables/farmacología , Animales , Antivirales/farmacología , Bovinos , Línea Celular , Farmacorresistencia Viral , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Replicación Viral/efectos de los fármacos
6.
Phytomedicine ; 21(11): 1432-8, 2014 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-25022206

RESUMEN

UNLABELLED: Propolis Extract ACF(®) (PPE) is a purified extract manufactured from propolis collected in a Canadian region rich in poplar trees, and it is the active substance of a topical ointment used against herpes labialis (cold sores or fever blisters). Aim of this study was to analyze the chemical composition of PPE in order to understand the plant origin and possible relations between compounds and antiviral activity, and to characterize the antiviral activity of the extract against herpes simplex virus in vitro. MATERIAL AND METHODS: The analysis of the propolis extract samples was conducted by Gas Chromatography-Mass Spectrometry (GC-MS). The antiviral activity was tested against herpes simplex viruses type 1 and type 2 in MDBK cell cultures by treating the cells with PPE at the time of virus adsorption, and by incubating the virus with the extract before infection (virucidal assay). RESULTS: Results from the GC-MS analyses revealed a dual plant origin of PPE, with components derived from resins of two different species of poplar. The chemical composition appeared standardized between extract samples and was also reproduced in the sample of topical ointment. The antiviral studies showed that PPE had a pronounced virucidal effect against herpes simplex viruses type 1 and type 2, and also interfered with virus adsorption.


Asunto(s)
Antivirales/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Própolis/farmacología , Animales , Antivirales/química , Canadá , Bovinos , Línea Celular , Cromatografía de Gases y Espectrometría de Masas , Pomadas/química , Populus/química , Própolis/química
7.
Biomed Res Int ; 2014: 920723, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24949484

RESUMEN

Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants--CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.


Asunto(s)
Nefropatía de los Balcanes/genética , Proteoglicanos de Heparán Sulfato/genética , Fallo Renal Crónico/genética , Elastasa Pancreática/genética , Canales de Potasio de Dominio Poro en Tándem/genética , Nefropatía de los Balcanes/patología , Exoma/genética , Predisposición Genética a la Enfermedad , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Fallo Renal Crónico/patología
8.
Antiviral Res ; 89(2): 174-81, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21134403

RESUMEN

The effects of combinations of three nonahydroxyterphenoyl-bearing C-glucosidic ellagitannins (castalagin, vescalagin and grandinin) with acyclovir (ACV) on the replication of type-1 and type-2 herpes simplex viruses in MDBK cells were tested by the focus-forming units reduction test. Ellagitannins included in these combinations possess a high individual antiviral activity: selectivity index of castalagin and vescalagin versus HSV-1 was similar to that of ACV, and relatively lower against HSV-2. The three-dimensional analytical approach of Prichard and Shipman was used to evaluate the impact of drug-drug interactions. The combination effects of ellagitannins with acyclovir were markedly synergistic.


Asunto(s)
Aciclovir/farmacología , Antivirales/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Taninos Hidrolizables/farmacología , Animales , Bovinos , Línea Celular , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana/métodos , Replicación Viral/efectos de los fármacos
9.
Acta Virol ; 53(1): 57-60, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19301953

RESUMEN

Standard therapies such as surgery and chemotherapy offer only minimal improvement in pancreatic cancer. However, the viruses killing cancer cells and substances like some antibiotics and phytoalexins with anticancer potential may represent a candidate non-conventional mean of cancer treatment in the future. In this study, the effect of infection with oncolytic H-1 parvovirus (H-1PV) combined with antibiotic norfloxacin (NFX) or phytoalexin resveratrol on the survival of cell lines Panc-1 and BxPC3 derived from human pancreatic carcinoma was tested. Whereas H-1PV with NFX exerted a synergistic effect, H-1PV with resveratrol resulted in an additive effect only. All the effects were partial, but they were more pronounced in Panc-1 compared to BxPC3 cells.


Asunto(s)
Antineoplásicos/farmacología , Parvovirus H-1/crecimiento & desarrollo , Virus Oncolíticos/crecimiento & desarrollo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Interacciones Farmacológicas , Humanos , Norfloxacino/farmacología , Resveratrol , Estilbenos/farmacología
10.
Bioorg Med Chem ; 16(15): 7457-61, 2008 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-18590964

RESUMEN

The aporphine alkaloid glaucine has been converted into 3-aminomethylglaucine and its free amino group has been linked to cinnamic, ferulic, sinapic, o-, and p-coumaric acids. The antioxidative potential of the synthesized amides was studied against DPPH(*) test. All of the tested compounds demonstrated higher radical scavenging activity than glaucine and 3-aminomethylglaucine, and lower antioxidative effect than the free hydroxycinnamic acids. The newly synthesized compounds were tested in vitro for antiviral activity against viruses belonging to different taxonomic groups.


Asunto(s)
Antioxidantes/química , Antivirales/química , Aporfinas/química , Cinamatos/química , Ácidos Cumáricos/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antioxidantes/farmacología , Antivirales/farmacología , Línea Celular , Perros , Humanos , Estructura Molecular , Relación Estructura-Actividad , Virus/efectos de los fármacos
11.
Protein Pept Lett ; 14(9): 917-22, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18045234

RESUMEN

A series of new peptidomimetics based on the tripeptide sequence Z-Leu-Phe-Gln-OH were synthesized, with ten of these including the alpha-nitrogen atom of the N-terminal amino acid incorporated into the pyrrole cycle. The synthesized compounds were tested for antiviral activity by agar-diffusion plaque inhibition test against Coxsackievirus B1 replication in FL cell. Four of the products were observed to possess an antiviral activity, which was proven to be significant for one product. N-terminal pyrrole moiety and C-terminal free carboxyl function are available in all active compounds. On the other hand, their corresponding -OBzl and -Obu t esters are inactive.


Asunto(s)
Antivirales/síntesis química , Antivirales/farmacología , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/farmacología , Diseño de Fármacos , Péptidos/química , Picornaviridae/efectos de los fármacos , Agar , Antivirales/química , Materiales Biomiméticos/química , Línea Celular , Enterovirus Humano B/efectos de los fármacos , Enterovirus Humano B/crecimiento & desarrollo , Glutamina/química , Humanos , Leucina/química , Fenilalanina/química , Picornaviridae/crecimiento & desarrollo , Relación Estructura-Actividad , Ensayo de Placa Viral
12.
J Hosp Infect ; 62(1): 98-106, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16307826

RESUMEN

A new formula with reduced ethanol content (55%) in combination with 10% propan-1-ol, 5.9% propan-1.2-diol, 5.7% butan-1.3-diol and 0.7% phosphoric acid exhibited a broad spectrum of virucidal activity. In quantitative suspension tests, with and without protein load, this formulation reduced the infectivity titre of seven enveloped (influenza A and B, herpes simplex 1 and 2, bovine corona, respiratory syncytial, vaccinia, hepatitis B, bovine viral diarrhoea) and four non-enveloped (hepatitis A, polio, rota, feline calici) viruses >10(3)-fold within 30s. In comparative testing, only 95% ethanol showed similar levels of activity. In fingerpad tests, the formulation produced a log10 reduction factor of the titre of poliovirus type 1 (Sabin) of 3.04 in 30s compared with 1.32 by 60% propan-2-ol. Testing against feline calicivirus produced a log10 reduction factor of 2.38 by the test formulation; in contrast, the log10 reduction factors with 70% ethanol and 70% propan-1-ol were 0.68 and 0.70, respectively.


Asunto(s)
Antivirales/farmacología , Desinfectantes/farmacología , Etanol/análisis , Desinfección de las Manos/métodos , Virus/efectos de los fármacos , 1-Propanol/análisis , Adulto , Animales , Antivirales/química , Butanoles/análisis , Calicivirus Felino/efectos de los fármacos , Gatos , Bovinos , Línea Celular , Desinfectantes/química , Sinergismo Farmacológico , Femenino , Dedos/virología , Humanos , Masculino , Ácidos Fosfóricos/análisis , Poliovirus/efectos de los fármacos , Propilenglicol/análisis
13.
Methods Find Exp Clin Pharmacol ; 25(7): 521-4, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-14571281

RESUMEN

The present study provides direct experimental proof that the combination of influenza virus infection A/Aichi/2/68 (H3N3) with different models of oxidative stress, such as immobilization, cold and cold-restraint, is associated with graduated oxidative disturbances in the stomach of mice, despite the absence of virus replication and inflammation in this tissue. It was found that experimental influenza virus infection is accompanied with significant changes in gastric mucosal integrity, as well as an increase in the products of lipid peroxidation in the stomachs of mice. Preliminary exposure of mice to immobilization stress and subsequent inoculation of influenza virus did not significantly influence gastric ulceration or lipid peroxidation compared with infected mice. Cold stress resulted in a significant decrease in the index of stomach ulceration and did not influence the fluorescent products of lipid peroxidation and MDA compared with infected animals. The simultaneous application of cold-restraint stress and influenza virus infection provoked synergism in the activity of all factors on the parameters under investigation. Ulceration increased approximately two-fold, as did the amount of fluorescent products of lipid peroxidation and MDA, compared with influenza virus-infected and non-stressed animals.


Asunto(s)
Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Virus de la Influenza A , Peroxidación de Lípido , Infecciones por Orthomyxoviridae/complicaciones , Úlcera Gástrica/metabolismo , Animales , Frío , Inmovilización , Masculino , Ratones , Ratones Endogámicos ICR , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/virología , Estrés Oxidativo , Restricción Física , Úlcera Gástrica/etiología , Úlcera Gástrica/patología , Estrés Psicológico/complicaciones
14.
Methods Find Exp Clin Pharmacol ; 25(4): 259-64, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12808470

RESUMEN

Successful antioxidant treatment of the so-called "free radical diseases" has been reported in the literature. In this study we examined the preventive effect of vitamin E and vitamin C, alone and in combination, on the damage caused by influenza virus infection (IVI). Male mice (ICR), infected with influenza virus A/2/68/(H3N2) (1.5 of LD(50)), were administered single once-daily doses of vitamin E (60 mg/kg b.w.) and vitamin C (80 mg/kg b.w.) intraperitoneally (3 days before virus inoculation). On the 5th and 7th day, respectively, after virus inoculation, animals were decapitated. Monooxygenase enzyme activity (ethylmorphine N-demethylase, amidopyrin N-demethylase, analgin N-demethylase, aniline hydroxylase, cytochrome P-450 content and NADPH-cytochrome C reductase [CCR]) was determined in liver 9000 x g supernatant. Primary and secondary products of lipid peroxidation (LPO; conjugated dienes [CD] and TBA-reactive substances) were measured in blood plasma, lung and liver 9000 x g supernatant. Vitamin E effectively restored LPO-levels increased by IVI. The effect of vitamin C was similar, but slighter. The combination (vitamin E + C) had greater effect on LPO levels than their separate administration. P-450-dependent monooxygenase activity was significantly restored and more pronounced cytochrome P-450 content and NADPH-CCR activity was noted. The preventive effect of vitamin E was stronger than the effect of vitamin C, but the combination (vitamin E + C) had the strongest effect. The superior protective effect of the combination is probably due to vitamin C's repairing effect on vitamin E's tocopheroxyl radical.


Asunto(s)
Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Infecciones por Orthomyxoviridae/prevención & control , Vitamina E/uso terapéutico , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Quimioterapia Combinada , Virus de la Influenza A , Inyecciones Intraperitoneales , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Oxigenasas de Función Mixta/metabolismo , Infecciones por Orthomyxoviridae/enzimología , Infecciones por Orthomyxoviridae/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
15.
Comp Immunol Microbiol Infect Dis ; 25(1): 1-11, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11831742

RESUMEN

The influenza virus infection (A/Aichi/2/68) was associated with development of oxidative stress in lung and blood of mice, accompanied by an increase in levels of lipid peroxidation products (conjugated dienes and total malondialdehyde) and a decrease in endogenous amounts of natural antioxidant vitamin E. These effects were most pronounced on the 5th day after virus inoculation, in comparison with those on the 7th. Supplementation of mice with exogenous vitamin E before virus inoculation lead to lung and blood protection against lipid peroxidation. A marked decrease in lipid peroxidation products and an increase in vitamin E content was established in blood and lung on the 5th and 7th day after virus inoculation. The stabilizing effect of vitamin E is dose-dependent in blood and dose-independent in lung, and was most pronounced on the 5th day after virus inoculation in comparison with the 7th day.


Asunto(s)
Antioxidantes/farmacología , Virus de la Influenza A , Peroxidación de Lípido/efectos de los fármacos , Infecciones por Orthomyxoviridae/metabolismo , Vitamina E/farmacología , Animales , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Pulmón/metabolismo , Masculino , Malondialdehído/sangre , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Factores de Tiempo , Vitamina E/sangre , Vitamina E/metabolismo
18.
Z Naturforsch C J Biosci ; 55(9-10): 824-9, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11098838

RESUMEN

Influenza virus infection is associated with development of oxidative stress in lung and blood plasma, viz. increase of primary and secondary lipid peroxidation products. It was established that rimantadine treatment led to a decrease of the products of lipid peroxidation in tissues of mice experimentally infected with influenza virus A/Aichi/2/68 (H3N2). The effect is strongest in blood plasma (a decrease of about 50%) and weaker in the lung (about 20%). To elucidate the mechanism of this action of rimantadine, experiments were carried out with some model systems. The capability of rimantadine to scavenge superoxide radicals (scavenging properties) was studied in a system of xanthine-xanthine oxidase to generate superoxide. The amount of superoxide was measured spectrophotometrically by the NBT-test and chemiluminesce. Rimantadine does not show scavenging properties and its antioxidant effect observed in vivo, is not a result of its direct action on the processes of lipid peroxidation and/or interaction with antioxidant enzymes. The antioxidant properties of rimantadine were investigated by measurement of induced lipid peroxidation in a Fe2+ and (Fe2+ - EDTA) system with an egg liposomal suspension. Our findings with model systems do not prove an antioxidant or prooxidant effect of the drug on the processes of lipid peroxidation. Apparently, the observed antioxidant effect of rimantadine in vivo is not connected directly with free radical processes in the organism.


Asunto(s)
Antioxidantes/farmacología , Peroxidación de Lípido/efectos de los fármacos , Pulmón/fisiología , Infecciones por Orthomyxoviridae/fisiopatología , Rimantadina/farmacología , Animales , Depuradores de Radicales Libres/farmacología , Virus de la Influenza A , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Masculino , Ratones , Ratones Endogámicos ICR , Infecciones por Orthomyxoviridae/sangre , Ratas , Ratas Wistar , Superóxidos/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Xantina , Xantina Oxidasa
19.
Acta Virol ; 44(2): 73-8, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10989697

RESUMEN

Effects of enviroxime and disoxaril, inhibitors of replication of some picornaviruses with known mechanisms of action, alone or in combination, on replication of coxsackievirus B1 (CVB1) in FL cells and on experimental CVB1 infection in newborn mice were tested. The combination of enviroxime and disoxaril resulted in vitro in a synergistic interaction. Both compounds were administered in vivo, alone or in combination, daily by subcutaneous (s.c.) route since the day of virus inoculation till the 5th day post inoculation (p.i.). Our findings about the in vivo antiviral effects of the individual compounds correlated with those of other authors, i.e. disoxaril significantly reduced the virus-induced death (the minimum 50% effective dose (ED50) was 12.5 mg/kg; P = 0.0037), while enviroxime was not effective even when applied at a dose as high as 100 mg/kg (P = 0.264). However, when both the substances were combined, the same protective effect was achieved with concentrations of disoxaril two to four times lower than those of the drug administered alone. In this way a higher selectivity ratio was achieved. Namely, the combination of 50 mg/kg enviroxime and 3.125-6.25 mg/kg disoxaril was synergistic. Along with reduction in mortality a marked delay in the course of the disease was observed.


Asunto(s)
Antivirales/farmacología , Bencimidazoles/farmacología , Infecciones por Coxsackievirus/prevención & control , Enterovirus Humano B/efectos de los fármacos , Isoxazoles/farmacología , Animales , Línea Celular , Sinergismo Farmacológico , Humanos , Ratones , Ratones Endogámicos ICR , Oximas , Sulfonamidas , Replicación Viral/efectos de los fármacos
20.
Z Naturforsch C J Biosci ; 55(3-4): 292-4, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10817222

RESUMEN

1-(4-Morpholinomethyl)-tetrahydro-2(1H)-pyrimidinone (mopyridone) exhibited a marked activity against rubella virus (Judith and RA27/3 strains), a MIC50 value of 0.9 microM and selectivity ratio of 557.7 been found in the case of Judith strain. These data, in addition to the previous ones about its anti-alphavirus effects suggest the compound to be considered as a broad spectrum inhibitor of togavirus replication.


Asunto(s)
Antivirales/farmacología , Pirimidinonas/farmacología , Virus de la Rubéola/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Animales , Línea Celular , Cricetinae
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