Angel Galabov - Academia.edu (original) (raw)
Papers by Angel Galabov
Single application of the interferon inducer dipyridamole administered intraperitoneally or per o... more Single application of the interferon inducer dipyridamole administered intraperitoneally or per os demonstrated a marked antiviral effect in mice with experimentally induced alphavirus infection –Semliki Forest (SFV) virus-caused encephalitis, applied orally in influenza virus A/Puerto Rico/8/34 (H1N1) and B/Lee/40 – respiratory infections, and herpes simplex virus type 1, strains Lennett and Leningrad 2 – encephalitis, and HSV-1 strain Leningrad 2-caused skin infection. In brain and respiratory infections the antiviral activity was manifested via the protection index, a decrease in the cumulative mortality percentage, and by the prolongation of the mean survival time. In the HSV-1 dermatitis suppression of symptomatology was observed.
Annals of Antivirals & Antiretrovirals, 2018
Castalagin, a nonahydroxytriphenoyl-bearing C-glucosidic ellagitannin, manifested a marked viruci... more Castalagin, a nonahydroxytriphenoyl-bearing C-glucosidic ellagitannin, manifested a marked virucidal effect on HSV-1. This effect was markedly temperature and time dependent, being clearly higher at 37 °C than at room temperature: ∆log of 3.13 with 10 μM concentration of castalagin (MNC). Castalagin also suppressed HSV-1 particle attachment to MDBK cells. A signifi cant effect (∆log = 1.7) was found after 30 min of substance exposure and was increased at 60 min (∆log = 3.2). Castalagin effect on the production of virions during the HSV-1 replication cycle was studied using a time-of-addition experimental scheme at the one-step viral replication cycle design. The highest sensitivity to castalagin was recorded 0-3 h post virus inoculation. A substantially weaker effect was found at the 6-12 h time intervals. At 18-24 h, HSV-1 replication was unsusceptible to castalagin. Evidently, castalagin target is located in the earlier stages of the HSV-1 replication cycle.
Acta virologica, 2017
Activity of three photosensitizing phthalocyanine derivatives was tested for photodynamic inactiv... more 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.
Antiviral chemistry & chemotherapy, Jan 4, 2016
Chemotherapy is an important tool for controlling enterovirus infections, but clinically effectiv... more Chemotherapy is an important tool for controlling enterovirus infections, but clinically effective anti-enterovirus drugs do not currently exist, mainly due to the development of drug resistance. We investigated the combination effects of enterovirus replication inhibitors in order to limit this process. In previous studies, we showed the efficacy of consecutive alternating administration of the triple combinations disoxaril/guanidine/oxoglaucine and pleconaril/guanidine/oxoglaucine against coxsackievirus B1 infection in newborn mice. Drug sensitivity tests of the viral brain isolates showed that these drug combinations prevented the development of drug resistance. In the current study, we replaced guanidine-HCl with enteroviral RNA synthesis inhibitor MDL-860 to test the effect of a new triple combination-pleconaril/MDL-860/oxoglaucine-applied via consecutive alternating administration in newborn mice infected subcutaneously with 20 MLD50 of coxsackievirus B1. The pleconaril/MDL-86...
Antiviral Chemistry and Chemotherapy, 2015
Background Influenza is a highly contagious viral infection of the respiratory system. To attack ... more Background Influenza is a highly contagious viral infection of the respiratory system. To attack two processes involved in flu pathogenesis—viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza. Methods After inoculation of albino mice with 10 MLD50 (50% mouse lethal dose) of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied orally at three doses, 2.5 mg/kg, 1.25 mg/kg, and 0.625 mg/kg, for five days post infection. α-Tocopherol (120 mg/kg, in sunflower oil) was administered intraperitoneally. Three schemes of α-tocopherol five-day course were tested: onset five or two days before infection, or on the virus inoculation day. Results Strongly dose-dependent augmented antiviral effect of the combination α-tocopherol and 0.625 mg/kg oseltamivir was demonstrated when α-tocopherol was administered simultaneously with oseltamivir: a pro...
2010 IEEE Frontiers in Education Conference (FIE), 2010
This work-in-progress paper describes the math and engineering module of the Go Green Institute a... more This work-in-progress paper describes the math and engineering module of the Go Green Institute at Binghamton University. This institute is a 10-day summer program for middle school students and was developed in an effort to increase the level of understanding of the scientific aspects of environmental sustainability and to promote interest in science, technology, engineering, and math careers. The Go
PLoS ONE, 2013
To better define the structure and origin of the Bulgarian paternal gene pool, we have examined t... more To better define the structure and origin of the Bulgarian paternal gene pool, we have examined the Y-chromosome variation in 808 Bulgarian males. The analysis was performed by high-resolution genotyping of biallelic markers and by analyzing the STR variation within the most informative haplogroups. We found that the Y-chromosome gene pool in modern Bulgarians is primarily represented by Western Eurasian haplogroups with , 40% belonging to haplogroups E-V13 and I-M423, and 20% to R-M17. Haplogroups common in the Middle East (J and G) and in South Western Asia (R-L23*) occur at frequencies of 19% and 5%, respectively. Haplogroups C, N and Q, distinctive for Altaic and Central Asian Turkic-speaking populations, occur at the negligible frequency of only 1.5%. Principal Component analyses group Bulgarians with European populations, apart from Central Asian Turkic-speaking groups and South Western Asia populations. Within the country, the genetic variation is structured in Western, Central and Eastern Bulgaria indicating that the Balkan Mountains have been permeable to human movements. The lineage analysis provided the following interesting results: (i) R-L23* is present in Eastern Bulgaria since the post glacial period; (ii) haplogroup E-V13 has a Mesolithic age in Bulgaria from where it expanded after the arrival of farming; (iii) haplogroup J-M241 probably reflects the Neolithic westward expansion of farmers from the earliest sites along the Black Sea. On the whole, in light of the most recent historical studies, which indicate a substantial proto-Bulgarian input to the contemporary Bulgarian people, our data suggest that a common paternal ancestry between the proto-Bulgarians and the Altaic and Central Asian Turkic-speaking populations either did not exist or was negligible.
International Journal of Legal Medicine, 2011
Experimental and Toxicologic Pathology, 2006
The aim of this work is to study the effect of the flavonoids rutin and quercetin on hepatic mono... more The aim of this work is to study the effect of the flavonoids rutin and quercetin on hepatic monooxygenase activities in experimental influenza virus infection (EIVI). EIVI causes oxidative stress in the whole organism. This is confirmed by the rapidly increased concentrations of thiobarbituric reactive substances in influenza-infected mice: lungs-290%; blood plasma-more than 320%; liver-230%; brain-50%. Although known for their antioxidant activities, rutin and quercetin exhibit prooxidant effect in healthy and antioxidant activity in influenza-infected animals. The pretreatment with both flavonoids (20 mg/kg b.w.) restores oxidative damage mostly in the target organ of the infection as well as in the liver of all infected mice (lungs: rutin-30%, quercetin-40%, combination-45%; liver: rutin-12%; quercetin-40%; combination-50%). As far as EIVI causes oxidative stress, toxicosis and inhibition of the hepatic monooxygenase activity, it is important to study the effects of rutin and quercetin on these systems. Both flavonoids induce the level of cytochrome P-450 (rutin-13%, quercetin-30%, combination-22%) but inactivate NADPH-cytochrome c reductase, aminopyrine N-demethylase and analgin N-demethylase on the 5th day of EIVI. Probably, these flavonoids affect different components of the monooxygenase system. These effects could be explained with oxidative hepatic intoxication on the 5th critical day of EIVI as well as higher dose treatment. More data are needed on the antioxidant/prooxidant effects of rutin and quercetin, probably due to specific metabolic and physiological activities, chemical structure, etc.
BMC Nephrology, 2013
Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephrit... more Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. Methods We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian en...
Archives of Toxicology, 2002
The present study provides a direct experimental evidence that the combination of influenza A/ Ai... more The present study provides a direct experimental evidence that the combination of influenza A/ Aichi/2/68 (H3N2) infection with different models of ''oxidative stress'', such as immobilization, cold and cold-restraint, is associated with graduated oxidative disturbances in the liver of mice, despite the absence of virus and inflammation in this tissue. It was found that experimental influenza virus infection is accompanied with a significant increase of lipid peroxidation products, a decrease of natural antioxidants (vitamin E, glutathione) and cytochrome P-450, an inhibition of cytochrome c reductase and liver monooxygenases (analgin-Ndemethylase and amidopyrine-N-demethylase). Immobilization and cold stress, applied separately or in combination (cold-restraint), did not influence significantly any of the analysed parameters compared to those of the control group of non-infected mice. Preliminary exposure of mice to immobilization or cold stress and subsequent inoculation of influenza virus resulted in a significant increase of lipid peroxidation products and a significant decrease of vitamin E and reduced glutathione, compared with levels in control (non-infected) animals. Compared to influenza virus-infected and nonstressed animals, the changes in all these parameters were negligible. Immobilization or cold stress, applied in combination with influenza virus infection, partially prevented the suppressive effect of influenza virus on cytochrome P-450 and liver monooxygenases. A tendency towards normalization of these parameters to the control levels was observed. However, after application of cold-restraint plus influenza virus infection, the level of cytochrome P-450 and activity of cytochrome c reductase stayed markedly lower than in infected and non-stressed animals. The activities of liver monooxygenases were slightly increased compared with those of infected and non-stressed animals, but stayed relatively low compared to control (non-infected) mice. Combination of coldrestraint and influenza virus infection resulted in a greater synergistic increase of lipid peroxidation products and a greater synergistic decrease of vitamin E and reduced glutathione compared to controls, as well as to influenza virus-infected and non-stressed animals. Keywords Influenza virus infection AE Immobilization AE Cold-restraint stress AE Lipid peroxidation AE Antioxidants
Acta Cytologica, 2009
To evaluate the effectiveness of the short PCR fragment 10-line probe assay (SPF10-LiPA) system i... more To evaluate the effectiveness of the short PCR fragment 10-line probe assay (SPF10-LiPA) system in detection of human papillomavirus (HPV) in abnormal Papanicolaou-stained cervicovaginal smears. We included 20 abnormal Papanicolaou-stained cervicovaginal smears. Samples were tested for HPV DNA detection and genotyping using the SPF10-LiPA system. All samples amplified the INF150 gene control. In 2 of 20 cases, amplification of the viral sequences was negative. Of processed samples, 18 of 20 presented HPV infection; of them, 56% showed only 1 type of HPV infection; the remaining presented > or = 2 types of HPV (multiple infections). HPV16 was the most frequent specific viral in 60%, in single and multiple infections, followed by HPV18 (20%), HPV6 (10%) and HPV58 (10%). We also found HR-HPV45, 52, 58 and 68 and LR-HPV6, 11 and 70 viral DNA types. These multiple infections were detected with greater frequencies in atypical squamous cells of undetermined significance and in the low-grade squamous intraepithelial lesions. The SPF10-LiPA system is efficient, sensitive, fast and simple for detecting and genotyping HPV DNA in abnormal Papanicolaou-stained cervicovaginal smears, which could be enormously useful in routine investigation for better clinical management of the patient.
Biotechnology & Biotechnological Equipment
Vitamin E in Health and Disease, Oct 24, 2018
Influenza is an infectious disease causing huge medical and economic losses. Influenza pathogenes... more Influenza is an infectious disease causing huge medical and economic losses. Influenza pathogenesis is associated with two processes in the human body: (i) lung damage due to viral replication in the columnar ciliary epithelium of bronchi and bronchioles and (ii) inflammatory burst inducing an increase in reactive oxygen species generation that causes extensive damage in cellular membranes of the small vessels. The oxidative stress in influenza virus-infected organism provokes free-radical oxidation of unsaturated lipid chains in the cell membranes. As vitamin E is a lipid-soluble substance and possesses a hydrophobic tail, it tends to accumulate within lipid membranes. There, it acts as the most important chain breaker, reacting with lipid peroxyl radicals much faster than they can react with adjacent fatty acid side chains. Among the antioxidants tested in influenza virus infections in mice, vitamin E occupies the leading position because of its efficacy in preventing oxidative damage through its free-radical scavenging activity. Although vitamin E is not possessing specific antiviral action, its antioxidant effect probably plays important role in lung and liver protection. Attention should be paid to the synergistic character of antiviral effect of the combination vitamin E and oseltamivir. Vitamin E could be recommended as a component in multitarget influenza therapy.
Antiviral Chemistry & Chemotherapy, 2011
Folia Medica
Introduction: Due to the high prevalence of viral infections having no specific treatment and the... more Introduction: Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of Tanacetum vulgare L. against viral strains of three taxonomic groups, including agents that cause socially significant diseases in humans for which antiviral chemotherapy is indicated, namely coxsackievirus B1 (family Picornaviridae), herpes simplex virus type 1 (family Herpesviridae) and influenza A virus (family Orthomyxoviridae). Aim: The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant Tanacetum vulgare L. against some important human viruses for which antiviral chemotherapy is needed and to characterize extract for its antioxidant activity in vitro. Materials and methods: The crude aqueous ethanolic extract from aerial parts...
Kidney International, 2004
Scientific Reports, Apr 1, 2019
One of the best documented Indo-European civilizations that inhabited Bulgaria is the Thracians, ... more One of the best documented Indo-European civilizations that inhabited Bulgaria is the Thracians, who lasted for more than five millennia and whose origin and relationships with other past and present-day populations are debated among researchers. Here we report 25 new complete mitochondrial genomes of ancient individuals coming from three necropolises located in different regions of Bulgaria – Shekerdja mogila, Gabrova mogila and Bereketska mogila – dated to II-III millennium BC. The identified mtDNA haplogroup composition reflects the mitochondrial variability of Western Eurasia. In particular, within the ancient Eurasian genetic landscape, Thracians locate in an intermediate position between Early Neolithic farmers and Late Neolithic-Bronze Age steppe pastoralists, supporting the scenario that the Balkan region has been a link between Eastern Europe and the Mediterranean since the prehistoric time. Spatial Principal Component Analysis (sPCA) performed on Thracian and modern mtDNA sequences, confirms the pattern highlighted on ancient populations, overall indicating that the maternal gene pool of Thracians reflects their central geographical position at the gateway of Europe.
Single application of the interferon inducer dipyridamole administered intraperitoneally or per o... more Single application of the interferon inducer dipyridamole administered intraperitoneally or per os demonstrated a marked antiviral effect in mice with experimentally induced alphavirus infection –Semliki Forest (SFV) virus-caused encephalitis, applied orally in influenza virus A/Puerto Rico/8/34 (H1N1) and B/Lee/40 – respiratory infections, and herpes simplex virus type 1, strains Lennett and Leningrad 2 – encephalitis, and HSV-1 strain Leningrad 2-caused skin infection. In brain and respiratory infections the antiviral activity was manifested via the protection index, a decrease in the cumulative mortality percentage, and by the prolongation of the mean survival time. In the HSV-1 dermatitis suppression of symptomatology was observed.
Annals of Antivirals & Antiretrovirals, 2018
Castalagin, a nonahydroxytriphenoyl-bearing C-glucosidic ellagitannin, manifested a marked viruci... more Castalagin, a nonahydroxytriphenoyl-bearing C-glucosidic ellagitannin, manifested a marked virucidal effect on HSV-1. This effect was markedly temperature and time dependent, being clearly higher at 37 °C than at room temperature: ∆log of 3.13 with 10 μM concentration of castalagin (MNC). Castalagin also suppressed HSV-1 particle attachment to MDBK cells. A signifi cant effect (∆log = 1.7) was found after 30 min of substance exposure and was increased at 60 min (∆log = 3.2). Castalagin effect on the production of virions during the HSV-1 replication cycle was studied using a time-of-addition experimental scheme at the one-step viral replication cycle design. The highest sensitivity to castalagin was recorded 0-3 h post virus inoculation. A substantially weaker effect was found at the 6-12 h time intervals. At 18-24 h, HSV-1 replication was unsusceptible to castalagin. Evidently, castalagin target is located in the earlier stages of the HSV-1 replication cycle.
Acta virologica, 2017
Activity of three photosensitizing phthalocyanine derivatives was tested for photodynamic inactiv... more 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.
Antiviral chemistry & chemotherapy, Jan 4, 2016
Chemotherapy is an important tool for controlling enterovirus infections, but clinically effectiv... more Chemotherapy is an important tool for controlling enterovirus infections, but clinically effective anti-enterovirus drugs do not currently exist, mainly due to the development of drug resistance. We investigated the combination effects of enterovirus replication inhibitors in order to limit this process. In previous studies, we showed the efficacy of consecutive alternating administration of the triple combinations disoxaril/guanidine/oxoglaucine and pleconaril/guanidine/oxoglaucine against coxsackievirus B1 infection in newborn mice. Drug sensitivity tests of the viral brain isolates showed that these drug combinations prevented the development of drug resistance. In the current study, we replaced guanidine-HCl with enteroviral RNA synthesis inhibitor MDL-860 to test the effect of a new triple combination-pleconaril/MDL-860/oxoglaucine-applied via consecutive alternating administration in newborn mice infected subcutaneously with 20 MLD50 of coxsackievirus B1. The pleconaril/MDL-86...
Antiviral Chemistry and Chemotherapy, 2015
Background Influenza is a highly contagious viral infection of the respiratory system. To attack ... more Background Influenza is a highly contagious viral infection of the respiratory system. To attack two processes involved in flu pathogenesis—viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza. Methods After inoculation of albino mice with 10 MLD50 (50% mouse lethal dose) of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied orally at three doses, 2.5 mg/kg, 1.25 mg/kg, and 0.625 mg/kg, for five days post infection. α-Tocopherol (120 mg/kg, in sunflower oil) was administered intraperitoneally. Three schemes of α-tocopherol five-day course were tested: onset five or two days before infection, or on the virus inoculation day. Results Strongly dose-dependent augmented antiviral effect of the combination α-tocopherol and 0.625 mg/kg oseltamivir was demonstrated when α-tocopherol was administered simultaneously with oseltamivir: a pro...
2010 IEEE Frontiers in Education Conference (FIE), 2010
This work-in-progress paper describes the math and engineering module of the Go Green Institute a... more This work-in-progress paper describes the math and engineering module of the Go Green Institute at Binghamton University. This institute is a 10-day summer program for middle school students and was developed in an effort to increase the level of understanding of the scientific aspects of environmental sustainability and to promote interest in science, technology, engineering, and math careers. The Go
PLoS ONE, 2013
To better define the structure and origin of the Bulgarian paternal gene pool, we have examined t... more To better define the structure and origin of the Bulgarian paternal gene pool, we have examined the Y-chromosome variation in 808 Bulgarian males. The analysis was performed by high-resolution genotyping of biallelic markers and by analyzing the STR variation within the most informative haplogroups. We found that the Y-chromosome gene pool in modern Bulgarians is primarily represented by Western Eurasian haplogroups with , 40% belonging to haplogroups E-V13 and I-M423, and 20% to R-M17. Haplogroups common in the Middle East (J and G) and in South Western Asia (R-L23*) occur at frequencies of 19% and 5%, respectively. Haplogroups C, N and Q, distinctive for Altaic and Central Asian Turkic-speaking populations, occur at the negligible frequency of only 1.5%. Principal Component analyses group Bulgarians with European populations, apart from Central Asian Turkic-speaking groups and South Western Asia populations. Within the country, the genetic variation is structured in Western, Central and Eastern Bulgaria indicating that the Balkan Mountains have been permeable to human movements. The lineage analysis provided the following interesting results: (i) R-L23* is present in Eastern Bulgaria since the post glacial period; (ii) haplogroup E-V13 has a Mesolithic age in Bulgaria from where it expanded after the arrival of farming; (iii) haplogroup J-M241 probably reflects the Neolithic westward expansion of farmers from the earliest sites along the Black Sea. On the whole, in light of the most recent historical studies, which indicate a substantial proto-Bulgarian input to the contemporary Bulgarian people, our data suggest that a common paternal ancestry between the proto-Bulgarians and the Altaic and Central Asian Turkic-speaking populations either did not exist or was negligible.
International Journal of Legal Medicine, 2011
Experimental and Toxicologic Pathology, 2006
The aim of this work is to study the effect of the flavonoids rutin and quercetin on hepatic mono... more The aim of this work is to study the effect of the flavonoids rutin and quercetin on hepatic monooxygenase activities in experimental influenza virus infection (EIVI). EIVI causes oxidative stress in the whole organism. This is confirmed by the rapidly increased concentrations of thiobarbituric reactive substances in influenza-infected mice: lungs-290%; blood plasma-more than 320%; liver-230%; brain-50%. Although known for their antioxidant activities, rutin and quercetin exhibit prooxidant effect in healthy and antioxidant activity in influenza-infected animals. The pretreatment with both flavonoids (20 mg/kg b.w.) restores oxidative damage mostly in the target organ of the infection as well as in the liver of all infected mice (lungs: rutin-30%, quercetin-40%, combination-45%; liver: rutin-12%; quercetin-40%; combination-50%). As far as EIVI causes oxidative stress, toxicosis and inhibition of the hepatic monooxygenase activity, it is important to study the effects of rutin and quercetin on these systems. Both flavonoids induce the level of cytochrome P-450 (rutin-13%, quercetin-30%, combination-22%) but inactivate NADPH-cytochrome c reductase, aminopyrine N-demethylase and analgin N-demethylase on the 5th day of EIVI. Probably, these flavonoids affect different components of the monooxygenase system. These effects could be explained with oxidative hepatic intoxication on the 5th critical day of EIVI as well as higher dose treatment. More data are needed on the antioxidant/prooxidant effects of rutin and quercetin, probably due to specific metabolic and physiological activities, chemical structure, etc.
BMC Nephrology, 2013
Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephrit... more Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. Methods We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian en...
Archives of Toxicology, 2002
The present study provides a direct experimental evidence that the combination of influenza A/ Ai... more The present study provides a direct experimental evidence that the combination of influenza A/ Aichi/2/68 (H3N2) infection with different models of ''oxidative stress'', such as immobilization, cold and cold-restraint, is associated with graduated oxidative disturbances in the liver of mice, despite the absence of virus and inflammation in this tissue. It was found that experimental influenza virus infection is accompanied with a significant increase of lipid peroxidation products, a decrease of natural antioxidants (vitamin E, glutathione) and cytochrome P-450, an inhibition of cytochrome c reductase and liver monooxygenases (analgin-Ndemethylase and amidopyrine-N-demethylase). Immobilization and cold stress, applied separately or in combination (cold-restraint), did not influence significantly any of the analysed parameters compared to those of the control group of non-infected mice. Preliminary exposure of mice to immobilization or cold stress and subsequent inoculation of influenza virus resulted in a significant increase of lipid peroxidation products and a significant decrease of vitamin E and reduced glutathione, compared with levels in control (non-infected) animals. Compared to influenza virus-infected and nonstressed animals, the changes in all these parameters were negligible. Immobilization or cold stress, applied in combination with influenza virus infection, partially prevented the suppressive effect of influenza virus on cytochrome P-450 and liver monooxygenases. A tendency towards normalization of these parameters to the control levels was observed. However, after application of cold-restraint plus influenza virus infection, the level of cytochrome P-450 and activity of cytochrome c reductase stayed markedly lower than in infected and non-stressed animals. The activities of liver monooxygenases were slightly increased compared with those of infected and non-stressed animals, but stayed relatively low compared to control (non-infected) mice. Combination of coldrestraint and influenza virus infection resulted in a greater synergistic increase of lipid peroxidation products and a greater synergistic decrease of vitamin E and reduced glutathione compared to controls, as well as to influenza virus-infected and non-stressed animals. Keywords Influenza virus infection AE Immobilization AE Cold-restraint stress AE Lipid peroxidation AE Antioxidants
Acta Cytologica, 2009
To evaluate the effectiveness of the short PCR fragment 10-line probe assay (SPF10-LiPA) system i... more To evaluate the effectiveness of the short PCR fragment 10-line probe assay (SPF10-LiPA) system in detection of human papillomavirus (HPV) in abnormal Papanicolaou-stained cervicovaginal smears. We included 20 abnormal Papanicolaou-stained cervicovaginal smears. Samples were tested for HPV DNA detection and genotyping using the SPF10-LiPA system. All samples amplified the INF150 gene control. In 2 of 20 cases, amplification of the viral sequences was negative. Of processed samples, 18 of 20 presented HPV infection; of them, 56% showed only 1 type of HPV infection; the remaining presented > or = 2 types of HPV (multiple infections). HPV16 was the most frequent specific viral in 60%, in single and multiple infections, followed by HPV18 (20%), HPV6 (10%) and HPV58 (10%). We also found HR-HPV45, 52, 58 and 68 and LR-HPV6, 11 and 70 viral DNA types. These multiple infections were detected with greater frequencies in atypical squamous cells of undetermined significance and in the low-grade squamous intraepithelial lesions. The SPF10-LiPA system is efficient, sensitive, fast and simple for detecting and genotyping HPV DNA in abnormal Papanicolaou-stained cervicovaginal smears, which could be enormously useful in routine investigation for better clinical management of the patient.
Biotechnology & Biotechnological Equipment
Vitamin E in Health and Disease, Oct 24, 2018
Influenza is an infectious disease causing huge medical and economic losses. Influenza pathogenes... more Influenza is an infectious disease causing huge medical and economic losses. Influenza pathogenesis is associated with two processes in the human body: (i) lung damage due to viral replication in the columnar ciliary epithelium of bronchi and bronchioles and (ii) inflammatory burst inducing an increase in reactive oxygen species generation that causes extensive damage in cellular membranes of the small vessels. The oxidative stress in influenza virus-infected organism provokes free-radical oxidation of unsaturated lipid chains in the cell membranes. As vitamin E is a lipid-soluble substance and possesses a hydrophobic tail, it tends to accumulate within lipid membranes. There, it acts as the most important chain breaker, reacting with lipid peroxyl radicals much faster than they can react with adjacent fatty acid side chains. Among the antioxidants tested in influenza virus infections in mice, vitamin E occupies the leading position because of its efficacy in preventing oxidative damage through its free-radical scavenging activity. Although vitamin E is not possessing specific antiviral action, its antioxidant effect probably plays important role in lung and liver protection. Attention should be paid to the synergistic character of antiviral effect of the combination vitamin E and oseltamivir. Vitamin E could be recommended as a component in multitarget influenza therapy.
Antiviral Chemistry & Chemotherapy, 2011
Folia Medica
Introduction: Due to the high prevalence of viral infections having no specific treatment and the... more Introduction: Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of Tanacetum vulgare L. against viral strains of three taxonomic groups, including agents that cause socially significant diseases in humans for which antiviral chemotherapy is indicated, namely coxsackievirus B1 (family Picornaviridae), herpes simplex virus type 1 (family Herpesviridae) and influenza A virus (family Orthomyxoviridae). Aim: The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant Tanacetum vulgare L. against some important human viruses for which antiviral chemotherapy is needed and to characterize extract for its antioxidant activity in vitro. Materials and methods: The crude aqueous ethanolic extract from aerial parts...
Kidney International, 2004
Scientific Reports, Apr 1, 2019
One of the best documented Indo-European civilizations that inhabited Bulgaria is the Thracians, ... more One of the best documented Indo-European civilizations that inhabited Bulgaria is the Thracians, who lasted for more than five millennia and whose origin and relationships with other past and present-day populations are debated among researchers. Here we report 25 new complete mitochondrial genomes of ancient individuals coming from three necropolises located in different regions of Bulgaria – Shekerdja mogila, Gabrova mogila and Bereketska mogila – dated to II-III millennium BC. The identified mtDNA haplogroup composition reflects the mitochondrial variability of Western Eurasia. In particular, within the ancient Eurasian genetic landscape, Thracians locate in an intermediate position between Early Neolithic farmers and Late Neolithic-Bronze Age steppe pastoralists, supporting the scenario that the Balkan region has been a link between Eastern Europe and the Mediterranean since the prehistoric time. Spatial Principal Component Analysis (sPCA) performed on Thracian and modern mtDNA sequences, confirms the pattern highlighted on ancient populations, overall indicating that the maternal gene pool of Thracians reflects their central geographical position at the gateway of Europe.