scholarly journals Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

2021 ◽  
Vol 14 (7) ◽  
pp. 686
Author(s):  
Raquel Porto ◽  
Ana C. Mengarda ◽  
Rayssa A. Cajas ◽  
Maria C. Salvadori ◽  
Fernanda S. Teixeira ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Screening Strategy ◽  
Early Infection ◽  
Global Public Health ◽  
Parasitic Worm ◽  
Electron Microscopy Analysis ◽  
Health Significance ◽  
Microscopy Analysis

The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.

Effects of Various Antioxidant Pretreatment Modalities on Adhesion to Sound and Caries-Affected Dentin: An In Vitro Study

2021 ◽  
pp. 232020682199798
Author(s):  
Beyza Unalan Degirmenci ◽  
Alperen Degirmenci ◽  
Emine Kara
Keyword(s):  
Bond Strength ◽  
In Vitro Study ◽  
Natural Antioxidants ◽  
Microtensile Bond Strength ◽  
Mandibular Molar ◽  
Electron Microscopy Analysis ◽  
Molar Teeth ◽  
Microscopy Analysis ◽  
Two Parameters

Aim: Natural antioxidants were offered as the answer of dentin adhesion issue. The aim of this study is to investigate the effects of proanthocyanidin and lycopene as pretreatment agents on the sound and caries-affected dentin surface on microtensile bond strength and microleakage. Materials and Methods: This study was designed as in vitro because of that 84 mandibular molar teeth were collected. Forty-two of the included teeth were carious teeth, while the other 42 were without caries. Sixty of them were used for microleakage and 24 for microtensile bond strength testing and scanning electron microscopy analysis. The samples were divided into six subgroups randomly according to dentin pretreatments: 5% proanthocyanidin, 5% lycopene, and no antioxidant application. After the restorative procedures, samples were attached to the microtensile tester. Samples were subjected to tensile stress in the load cell until they broke at a speed of 0.5 mm per min. Microtensile bond strength (µTBS) and microleakage test data were analyzed with two-way analysis of variance, Bonferroni correction, and Tamhane’s T2 tests. Results: Two-way variance analysis showed that dentin pretreatment applications, dentin substrate, and the interaction between these two parameters had statistically significant effects on µTBS values ( P < .001). There was no difference between dentin pretreatment applications in terms of microleakage scores ( P > .05). Conclusion: The application of dentin pretreatment with proanthocyanidin is a successful procedure that increases the bond strength in both dentin substrate, while pretreatment with lycopene in caries-affected dentin reduces it.

Schistosoma mansoni: evidence for a role of serum factors in protecting artificially transformed schistosomula against antibody-mediated killing in vitro

Parasitology ◽  
1978 ◽  
Vol 77 (2) ◽  
pp. 225-233 ◽  
Author(s):  
C. A. P. Tavares ◽  
Rita C. Soares ◽  
P. M. Z. Coelho ◽  
G. Gazzinelli
Keyword(s):  
Schistosoma Mansoni ◽  
Protective Factor ◽  
Gel Filtration ◽  
Defined Medium ◽  
Rabbit Serum ◽  
Chemically Defined Medium ◽  
Lethal Effects ◽  
Serum Factors

SummaryArtificially transformed schistosomula of Schistosoma mansoni develop a consistent but small protection against the lethal effects of antibody plus complement when cultured for 24 h in a chemically defined medium. In contrast, they become rapidly resistant to antibody plus complement, when cultured in the presence of a complex medium consisting of equal parts of heat-inactivated rabbit serum and Earle's/lactalbumin or in defined medium supplemented with small amounts of heat-inactivated rabbit serum. Sephadex G-200 gel filtration revealed that the protective factor in rabbit serum is a macromolecule with a molecular weight between 7 and 19S. Parasites cultured at 10 °C or in the presence of 200 μg of puromycin show less serum-induced protection against the lethal effects of antibody plus complement than do controls.

New GroEL-like chaperonin of bacteriophage OBP Pseudomonas fluorescens suppresses thermal protein aggregation in an ATP-dependent manner

2016 ◽  
Vol 473 (15) ◽  
pp. 2383-2393 ◽  
Author(s):  
Pavel I. Semenyuk ◽  
Victor N. Orlov ◽  
Olga S. Sokolova ◽  
Lidia P. Kurochkina
Keyword(s):  
Pseudomonas Fluorescens ◽  
Functional Characterization ◽  
Dependent Manner ◽  
Double Ring ◽  
Protein Inactivation ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis ◽  
Ring Architecture

Recently, we discovered and studied the first virus-encoded chaperonin of bacteriophage EL Pseudomonas aeruginosa, gene product (gp) 146. In the present study, we performed bioinformatics analysis of currently predicted GroEL-like proteins encoded by phage genomes in comparison with cellular and mitochondrial chaperonins. Putative phage chaperonins share a low similarity and do not form a monophyletic group; nevertheless, they are closer to bacterial chaperonins in the phylogenetic tree. Experimental investigation of putative GroEL-like chaperonin proteins has been continued by physicochemical and functional characterization of gp246 encoded by the genome of Pseudomonas fluorescens bacteriophage OBP. Unlike the more usual double-ring architecture of chaperonins, including the EL gp146, the recombinant gp246 produced by Escherichia coli cells has been purified as a single heptameric ring. It possesses ATPase activity and does not require a co-chaperonin for its function. In vitro experiments demonstrated that gp246 is able to suppress the thermal protein inactivation and aggregation in an ATP-dependent manner, thus indicating chaperonin function. Single-particle electron microscopy analysis revealed the different conformational states of OBP chaperonin, depending on the bound nucleotide.

Recognition and invasion of human skin by Schistosoma mansoni cercariae: the key-role of L-arginine

Parasitology ◽  
2002 ◽  
Vol 124 (2) ◽  
pp. 153-167 ◽  
Author(s):  
W. HAAS ◽  
K. GRABE ◽  
C. GEIS ◽  
T. PÄCH ◽  
K. STOLL ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Mouse Skin ◽  
Ventral Side ◽  
Body Axis ◽  
Surface Layers ◽  
Mammalian Skin ◽  
Cellular Immune ◽  
Arginine Concentration

The attachment of Schistosoma mansoni cercariae to mammalian skin is specifically stimulated by L-arginine. As L-arginine is an unsuitable signal for a specific identification of mammalian skin we examined the following 5 hypotheses to explain the advantage of the cercarial sensitivity to L-arginine. (1) A Schistosoma infection lowered the arginine concentration in the serum of mice, and this could enable the cercariae to avoid attachments to already infected mice. However, the infection did not reduce the arginine concentration in the skin and the cercarial attachment responses to it. (2) Creeping cercariae showed chemotactic orientation specifically along increasing L-arginine gradients. L-arginine could act as a pheromone which could guide cercariae towards common penetration sites. However, the cercarial acetabular gland contents were not attractive and they did not (in contrast to previous reports) contain much arginine. (3) Schistosomula (transformed cercariae) could use L-arginine to produce nitric oxide (NO) for blood vessel dilation during their migration in the host. However, in vitro the transformed cercariae did not convert L-arginine into citrulline and NO. (4) Schistosomula could bind L-arginine from the surrounding tissues and so escape the cellular immune attack (which needs L-arginine as the precursor of NO). However, transformed cercariae bound no more L-arginine than L-serine and L-lysine. (5) Schistosomula, migrating parallel to the surface in the mammalian epidermis, are dependent on information on their position between the inner and the surface layers of the skin. In the mouse skin, they adjusted their body axis with the ventral side toward the deeper (arginine-residue rich) epidermis layers. When migrating in agar, they showed chemo-orientation toward serum, and D-glucose and L-arginine were the stimulating compounds therein. The burrowing schistosomula adjusted their body axis (as in the epidermis) with the ventral side toward the higher concentration of L-arginine and not of glucose. We argue that the sensitivity for L-arginine has its primary function in orientation within mammalian skin and in location of blood vessels.

Production and characterization of titanium and iron oxide nano-sized thin films

2001 ◽  
Vol 16 (6) ◽  
pp. 1559-1564 ◽  
Author(s):  
E. Comini ◽  
G. Sberveglieri ◽  
M. Ferroni ◽  
V. Guidi ◽  
C. Frigeri ◽  
...  
Keyword(s):  
Thin Films ◽  
Iron Oxide ◽  
Gas Sensing ◽  
Iron Concentration ◽  
Radio Frequency Sputtering ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis ◽  
Reproducible Method

We present a simple and reproducible method to obtain TiO2 and Fe2O3 mixed-oxide thin films by reactive radio-frequency sputtering. The influence of iron concentration on the structural properties of the layers has been studied. Structural characterization, carried out by electron microscopy analysis, allowed one to correlate the inhibition of the grain growth of titania to the presence of iron oxide and to its segregation at grain boundaries. This behavior should be ascribed to a superficial-tension phenomenon. As a possible application of these thin films, we have investigated the gas-sensing properties toward CO, with particular focus on the role of Fe. The layers were capable to sense CO down to the level requested for environmental monitoring.

scholarly journals Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein

2020 ◽  
Author(s):  
Dongchun Ni ◽  
Kelvin Lau ◽  
Frank Lehmann ◽  
Andri Fränkl ◽  
David Hacker ◽  
...  
Keyword(s):  
Structural Rearrangement ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Cryo Electron Microscopy ◽  
Monomeric Complex ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis ◽  
Viral Surface

AbstractThe human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, the role of hACE2 for virus fusion is not well understood. Blocking the transition of Spike from its prefusion to post-fusion state might be a strategy to prevent or treat COVID-19. Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. This observed hACE2 dependent dissociation of the Spike trimer suggests a mechanism for the therapeutic role of recombinant soluble hACE2 for treatment of COVID-19.

scholarly journals Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19

2020 ◽  
Author(s):  
Douglas Ferreira Sales-Medina ◽  
Ludmila Rodrigues Pinto Ferreira ◽  
Lavínia M. D. Romera ◽  
Karolina Ribeiro Gonçalves ◽  
Rafael V. C. Guido ◽  
...  
Keyword(s):  
Network Analysis ◽  
Virus Transmission ◽  
Drug Repurposing ◽  
Abiraterone Acetate ◽  
Screening Strategy ◽  
Phenotypic Screening ◽  
Global Public Health ◽  
Screening Assay ◽  
Hedera Helix

AbstractThe disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug-host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection.Summary sentenceDiscovery of drug repurposing candidates, inhibitors of SARS-CoV-2 infection in vitro, using a phenotypic screening strategy and network analysis.

scholarly journals Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mariana G. de Brito ◽  
Ana C. Mengarda ◽  
George L. Oliveira ◽  
Maria E. Cirino ◽  
Tais C. Silva ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Chronic Infection ◽  
Worm Burden ◽  
Egg Production ◽  
Laser Scanning Microscopy ◽  
Early Infection ◽  
Blood Fluke ◽  
Serum Aminotransferase ◽  
Content Type

ABSTRACT Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma. Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against Schistosoma mansoni ex vivo and in mice harboring either chronic or early S. mansoni infections. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg of body weight) or by oral gavage (100 to 400 mg/kg), and we studied the influence of the drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro, 50% effective concentrations (EC50) and EC90 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by Schistosoma eggs.

Sorbinil, an Aldose Reductase Inhibitor, in Fighting Against Diabetic Complications

2019 ◽  
Vol 15 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Qi Huang ◽  
Qiong Liu ◽  
Dongsheng Ouyang
Keyword(s):  
Aldose Reductase ◽  
Diabetic Complications ◽  
Polyol Pathway ◽  
Review Article ◽  
Global Public Health ◽  
Model Studies ◽  
Human Use ◽  
Pathway Inhibition

Background: Aldose reductase (AR) is involved in the pathogenesis of diabetes, which is one of the major threats to global public health. Objective: In this review article, we have discussed the role of sorbinil, an AR inhibitor (ARI), in preventing diabetic complications. Results: AR contributes in diabetes by generating excess intracellular superoxide and other mediators of oxidative stress through polyol pathway. Inhibition of AR activity thus might be a potential approach for the management of diabetic complications. Experimental evidences indicated that sorbinil can decrease AR activity and inhibit polyol pathway. Both in vitro and animal model studies reported the efficacy of sorbinil in controlling the progression of diabetes. Moreover, Sorbinil has been found to be comparatively safer than other ARIs for human use. But, it is still in earlyphase testing for the treatment of diabetic complications clinically. Conclusion: Sorbinil is an effective ARI, which could play therapeutic role in treating diabetes and diabetic complications. However, advanced clinical trials are required for sorbinil so that it could be applied with the lowest efficacious dose in humans.

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