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1.
Environ Monit Assess ; 193(9): 606, 2021 Aug 28.
Article in English | MEDLINE | ID: mdl-34453609

ABSTRACT

The collapse of mining tailing dams in Brumadinho, Minas Gerais, Brazil, that occurred in 2019 was one of the worst environmental and social disasters witnessed in the country. In this sense, monitoring any impacted areas both before and after the disaster is crucial to understand the actual scenario and problems of disaster management and environmental impact assessment. In order to find answers to that problem, the aim of this study was to identify and analyze the spatiality of the impacted area by rupture of the tailing dam of the Córrego do Feijão mine in Brumadinho, Minas Gerais, by using orbital remote sensing. Land use and land occupation, phytoplankton chlorophyll-a, water turbidity, total suspended solids on water, and carbon sequestration efficiency by vegetation (CO2Flux) were estimated by orbital imagery from the Landsat-8/OLI and MSI/Sentinel-2 sensors in order to assess the environmental impacts generated by the disaster. Data were extracted from spectral models in which the variables that best demonstrated the land use variation over the years were sought. Mean comparison by t-test was performed to compare the time series analyzed, that is, before and after the disaster. Through the analysis of water quality, it was observed that the environmental impact was calamitous to natural resources, especially water from Córrego do Feijão.


Subject(s)
Environmental Monitoring , Remote Sensing Technology , Brazil , Environment , Mining
2.
Intervirology ; 62(2): 80-89, 2019.
Article in English | MEDLINE | ID: mdl-31315128

ABSTRACT

BACKGROUND: In immunocompromised patients, human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality. Suppressor of cytokine signaling (SOCS) proteins are very potent negative regulators of the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. We hypothesized that HCMV exploits SOCS1 and/or SOCS3 to its advantage. METHODS: All experiments were carried out with primary human lung-derived microvascular endothelial cells (HMVEC). SOCS1 and SOCS3 were silenced by transfecting the cells with siRNA. HCMV was propagated and titered on human lung-derived fibroblasts MRC5. Real-time PCR and Western blot were used to detect mRNA and protein levels, respectively. RESULTS: The data presented show that an efficient replication of HCMV in HMVEC is dependent on SOCS3 protein. Time course analysis revealed an increase in SOCS3 protein levels in infected cells. Silencing of SOCS3 (siSOCS3) resulted in inhibition of viral immediate early, early, and late antigen production. Consistently, HCMV titers produced by siSOCS3 cultures were significantly decreased when compared to control transfected cultures (siCNTRs). STAT1 and STAT2 phosphorylation was increased in siSOCS3-infected cells when compared to siCNTR-treated cells. CONCLUSION: These findings indicate the implication of SOCS3 in the mechanism of HCMV-mediated control of cellular immune responses.


Subject(s)
Cytomegalovirus/physiology , Endothelial Cells/virology , Immunity, Cellular , Suppressor of Cytokine Signaling 3 Protein/immunology , Virus Replication , Cells, Cultured , Endothelial Cells/immunology , Gene Silencing , Humans , Lung/cytology , Lung/virology , Phosphorylation , RNA, Small Interfering , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/immunology , Signal Transduction/immunology , Suppressor of Cytokine Signaling 1 Protein/genetics , Suppressor of Cytokine Signaling 1 Protein/immunology , Suppressor of Cytokine Signaling 3 Protein/genetics
3.
J Med Virol ; 87(1): 141-53, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24976258

ABSTRACT

Vasculoprotective and cholesterol-lowering properties are hallmarks of statins. Recently, statins have been found to exhibit antiviral activity. Little is known about the potential of statins against human cytomegalovirus (HCMV), a risk factor in the pathogenesis of atherosclerosis. In this study, the in vitro anti-CMV activity of four statins (atorva-, fluva-, prava-, and simvastatin) was explored in human aortic endothelial cells (HAEC) and fibroblasts. All statins dose-dependently reduced HCMV titers in both cell types. Whereas atorva-, fluva-, and simvastatin showed comparable EC50 and EC90 within a low micromolar range in HAEC, pravastatin exhibited only limited effects. In metabolite rescue experiments, mevalonate almost completely abrogated the anti-CMV activity of all statins, whereas cholesterol failed to counteract the effects. Geranylgeranyl-pyrophosphate partially reversed the anti-CMV activity of most statins, suggesting an involvement of the non-sterol isoprenoid arm of the mevalonate pathway as the mode-of-action. The accumulation of immediate early viral antigens was blocked after 1 dpi onwards, and early and late antigen expression was completely abolished in HAEC. The antiviral activity of statins was comparable to ganciclovir and was retained in a ganciclovir-resistant HCMV strain. These findings provide new insight into the beneficial effects of statins, adding antiviral activity against HCMV to their list of pleïotropic properties, and support further clinical investigations on combined therapy for the management of active HCMV disease.


Subject(s)
Anticholesteremic Agents/pharmacology , Antiviral Agents/pharmacology , Cytomegalovirus/drug effects , Cells, Cultured , Cholesterol/metabolism , Drug Resistance, Viral , Endothelial Cells , Fibroblasts , Ganciclovir/pharmacology , Humans , Mevalonic Acid/metabolism , Microbial Sensitivity Tests , Polyisoprenyl Phosphates/metabolism
4.
Xenotransplantation ; 21(4): 324-40, 2014.
Article in English | MEDLINE | ID: mdl-24712388

ABSTRACT

BACKGROUND: Primary infection and reactivation of human cytomegalovirus (HCMV) is associated with allograft rejection. Pig-to-human xenotransplantation is regarded as an alternative to circumvent donor organ shortage and inevitably, porcine endothelial cells (pEC) will be exposed to human pathogens, among them HCMV. Infection of pEC with HCMV induces apoptosis and entry is sufficient to induce phenotypic alterations, which have the potential to result in rejection and vasculopathy. We investigated the mechanisms used by HCMV to enter pEC from different anatomical origins and compared them with the entry mechanisms used to enter human endothelial cells (hEC). METHODS: Immortalized porcine aortic (PEDSV.15) and porcine microvascular bone marrow derived EC (2A2) as well as primary human aortic (HAEC) and microvascular EC (HMVEC) were inoculated with the endotheliotropic (TB40/E) or the fibroblast propagated (TB40/F) HCMV strains at multiplicity of infection (MOI) ranging from 0.3 to 5. EC were analyzed for receptor expression and their involvement in HCMV entry. The role of endocytosis was evaluated by treating EC with specific inhibitors, and the involvement of the endolysosomal pathway was investigated by confocal microscopy. RESULTS: Silencing of platelet-derived growth factor receptor alpha resulted in a reduced expression of viral immediate early (IE) antigen only in pEC infected with either TB40/E or TB40/F whereas silencing of ß1 integrins reduced expression of IE proteins in all EC except for TB40/F-infected microvascular pEC. TB40/E enters hEC and pEC by a similar mechanism dependent on dynamin-2, lipid rafts, actin and pH, whereas entry of TB40/F in pEC occurs mainly by a dynamin-2-dependent, clathrin-, lipid rafts-independent mechanism and in a pH-dispensable manner. When actin polymerization was prevented, TB40/F could enter pEC in an actin-independent fashion. Disturbance of the microtubule cytoskeleton resulted in an inhibition of infection of TB40/E-infected EC, whereas infection of TB40/F-infected pEC was not modified. Finally, viral particles located in vesicles of the endolysosomal pathway, suggesting that HCMV uses this pathway for intracellular trafficking following entry. CONCLUSIONS: Our findings demonstrate that HCMV uses a variety of entry mechanisms that are dependent on the strain and on the vascular origin of the cells. Given the profound effect of pEC infection with HCMV, prevention of such an infection will be crucial for clinical application of xenotransplantation. A potential avenue is to render porcine grafts resistant to HCMV infection by blocking viral entry and propagation.


Subject(s)
Cytomegalovirus/physiology , Cytomegalovirus/pathogenicity , Endothelial Cells/virology , Transplantation, Heterologous/adverse effects , Actins/metabolism , Animals , Cells, Cultured , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Infections/transmission , Cytomegalovirus Infections/virology , Dynamin II/metabolism , Endocytosis , Endothelial Cells/metabolism , ErbB Receptors/metabolism , Humans , Hydrogen-Ion Concentration , Integrins/metabolism , Membrane Microdomains/metabolism , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Receptors, Virus/metabolism , Species Specificity , Sus scrofa , Virus Internalization
5.
Chem Biol Drug Des ; 76(5): 451-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20880017

ABSTRACT

This work reports the preparation of several amino alcohols condensed with d-arabinose, d-glucose, and d-galactose derivatives. These compounds were evaluated in vitro for their cytotoxicity and ability to decrease nitric oxide production in J774A.1 cells. Arabinofuranoside derivatives 5a, 5b and 5c showed a significant inhibition of nitric oxide production (>80% at 5 µg/mL), while the galactopyranoside derivative 8d showed a notable nitric oxide inhibitory activity (126% at 0.5 µg/mL).


Subject(s)
Amino Alcohols/chemistry , Carbohydrates/chemistry , Nitric Oxide/metabolism , Amino Alcohols/chemical synthesis , Amino Alcohols/toxicity , Animals , Arabinose/chemistry , Cell Line, Tumor , Galactose/chemistry , Glucose/chemistry , Interferon-gamma/pharmacology , Lipopolysaccharides/pharmacology , Mice
6.
Chem Biol Drug Des ; 75(2): 233-5, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20028395

ABSTRACT

In this work, a number of lipidic amino alcohols wereas synthesized and evaluated in vitro on cultures of Leishmania amazonensis and Leishmania chagasi. Nine amino alcohols showed inhibition of L. chagasi growth, and seven of them showed inhibition of L. amazonensis with IC(50) below 10 microm. Compound 11f was more active than the reference drug amphotericin B against L. chagasi promastigote forms.


Subject(s)
Amino Alcohols/chemical synthesis , Leishmania/drug effects , Trypanocidal Agents/chemical synthesis , Amino Alcohols/chemistry , Amino Alcohols/pharmacology , Amphotericin B/pharmacology , Humans , Leishmania/growth & development , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology
7.
Mem Inst Oswaldo Cruz ; 104(5): 703-5, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19820828

ABSTRACT

A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol were synthesized and tested for their antitubercular activity. Compounds 3, 8 and 9 were found to be the most active (MIC of 6.25 microg/mL). Nine other compounds displayed activity against Mycobacterium tuberculosis, with a MIC of 12.5 microg/mL.


Subject(s)
Amino Alcohols/pharmacology , Antitubercular Agents/pharmacology , Diamines/pharmacology , Mycobacterium tuberculosis/drug effects , Amino Alcohols/chemical synthesis , Antitubercular Agents/chemistry , Diamines/chemical synthesis , Microbial Sensitivity Tests
8.
Mem. Inst. Oswaldo Cruz ; 104(5): 703-705, Aug. 2009. ilus, tab
Article in English | LILACS | ID: lil-528076

ABSTRACT

A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol were synthesized and tested for their antitubercular activity. Compounds 3, 8 and 9 were found to be the most active (MIC of 6.25 µg/mL). Nine other compounds displayed activity against Mycobacterium tuberculosis, with a MIC of 12.5 µg/mL.


Subject(s)
Amino Alcohols/pharmacology , Antitubercular Agents/pharmacology , Diamines/pharmacology , Mycobacterium tuberculosis/drug effects , Amino Alcohols/chemical synthesis , Antitubercular Agents/chemistry , Diamines/chemical synthesis , Microbial Sensitivity Tests
9.
Bioorg Med Chem ; 15(24): 7789-94, 2007 Dec 15.
Article in English | MEDLINE | ID: mdl-17851083

ABSTRACT

A series of N- and C-alkylated amino alcohols and of their protected galactopyranosyl derivatives was synthesized and evaluated for antitubercular activity. Five of these compounds displayed good activity, with a MIC below 12.5mug/mL. The presence of the carbohydrate slightly affected the antibacterial activity.


Subject(s)
Amino Alcohols/chemical synthesis , Amino Alcohols/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Alkylation , Amino Alcohols/chemistry , Antitubercular Agents/chemistry , Cell Proliferation , Cells, Cultured , Glycosylation , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
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