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1.
iScience ; 27(9): 110765, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39286499

RESUMO

Fast and efficient galvanostatic conversion of 2,4-diarylfurans into dimeric furan-2(5H)-ones is now possible in one pot and good yields at room temperature in sustainable aqueous organic solvent. Recent applications of these highly desired structures demand our attention since they are a versatile alternative to acrylates in polymerization to achieve green materials. The reaction mechanism proposal, supported by density functional theory (DFT) theoretical calculations, involves furanoxy radicals, detected by electron paramagnetic resonance (EPR), as the last intermediate before a homocoupling step that affords butenolides. The process can be successfully extended to an array of electron-donating and electron-withdrawing substituents on the aromatic ring. The proposed pathways to explain the formation of the products are rationalized and discussed. A concomitant oxidation of water to hydroxyl radicals is not discarded, particularly with electron-withdrawing substituents at the aromatic ring. In addition, the biological activity as biocides of the obtained compounds was tested, and they showed promising activity against Staphylococcus aureus.

2.
Liver Int ; 44(9): 2409-2423, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38847511

RESUMO

BACKGROUND AND AIMS: Cyclooxygenase-2 (COX-2) is involved in different liver diseases, but little is known about the significance of COX-2 in cholestatic injury. This study was designed to elucidate the role of COX-2 expression in hepatocytes during the pathogenesis of obstructive cholestasis. METHODS: We used genetically modified mice constitutively expressing human COX-2 in hepatocytes. Transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were either subjected to a mid-abdominal laparotomy or common bile duct ligation (BDL) for 2 or 5 days. Then, we explored the mechanisms underlying the role of COX-2 and its derived prostaglandins in liver function, and the synthesis and excretion of bile acids (BA) in response to cholestatic liver injury. RESULTS: After BDL, hCOX-2-Tg mice showed lower grades of hepatic necrosis and inflammation than Wt mice, in part by a reduced hepatic neutrophil recruitment associated with lower mRNA levels of pro-inflammatory cytokines. Furthermore, hCOX-2-Tg mice displayed a differential metabolic pattern of BA synthesis that led to an improved clearance after BDL-induced accumulation. In addition, an enhanced response to the BDL-induced oxidative stress and hepatic apoptosis was observed. In vitro experiments using hepatic cells that stably express hCOX-2 confirmed the cytoprotective role of prostaglandin E2 against BA toxicity. CONCLUSIONS: Taken together, our data indicate that constitutive expression of COX-2 in hepatocytes ameliorates cholestatic liver injury in mice by reducing inflammation and cell damage and by modulating BA metabolism, pointing to a role for COX-2 as a defensive response against cholestasis-derived BA accumulation and injury.


Assuntos
Ácidos e Sais Biliares , Colestase , Ducto Colédoco , Ciclo-Oxigenase 2 , Hepatócitos , Fígado , Camundongos Transgênicos , Animais , Humanos , Masculino , Camundongos , Apoptose , Ácidos e Sais Biliares/metabolismo , Colestase/metabolismo , Ducto Colédoco/cirurgia , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Modelos Animais de Doenças , Hepatócitos/metabolismo , Ligadura , Fígado/patologia , Fígado/metabolismo , Estresse Oxidativo
3.
Int J Mol Sci ; 25(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38612821

RESUMO

Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and different inorganic ligands: chloride, nitrate, and acetate. The antibacterial effect of the Zn(II) complexes was studied against planktonic bacterial cells of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) strains. The results showed a moderate biocide activity in both types of planktonic bacteria, which arises from the metal complexation to the Schiff base ligand. Importantly, we confirmed the crucial effect of the metal, with Zn(II) improving the activity of Cu(II) counterparts previously reported. On the other hand, the impact of the inorganic ligands was not significant for the antibacterial effect but was relevant for the complex solubility. Finally, as proof of concept of topical antibacterial formulation, we formulated an emulsion containing the most lipophilic Zn(II) complex and confirmed a sustained release for 24 h in a vertical cell diffusion assay. The promising activity of iminopyridine Zn(II) complexes is potentially worth exploring in more detailed studies.


Assuntos
Complexos de Coordenação , Zinco , Zinco/farmacologia , Ligantes , Bases de Schiff/farmacologia , Nitratos , Complexos de Coordenação/farmacologia , Antibacterianos/farmacologia , Escherichia coli , Plâncton
4.
Pathogens ; 13(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38535549

RESUMO

Daptomycin is one of the last therapeutic resources for multidrug-resistant gram-positive bacteria. Despite its structural similarities with glycopeptides, its mechanisms of action and resistance are different and in some respects are not completely understood. Mutations in several genes have been associated with daptomycin resistance, especially in mprF, walkR, rpoB and rpoC, but their role and importance remain to be elucidated. We have studied mutations in 11 genes, which have been previously associated with daptomycin non-susceptibility, in nine daptomycin-non-susceptible Staphylococcus aureus clinical isolates (daptomycin MIC: >1 mg/L). Susceptibility to daptomycin, vancomycin, linezolid, oxacillin, telavancin and dalbavancin was studied. walkR, agrA, cls1, cls2, fakA, pnpA, clpP, prs, rpoB, rpoC and mprF were amplified by PCR and sequenced. The sequences were compared with the S. aureus ATCC 25923 complete genome (GenBank gi: 685631213) by using BLAST® software. We did not find any changes in walkR, pnpA, prs and clpP. All isolates excepting isolate MSa5 showed a high number of significant mutations (between 13 and 25 amino acid changes) in mprF. Most isolates also showed mutations in the rpo genes, the cls genes and fakA. Daptomycin non-susceptibility in S. aureus clinical isolates seems to be reached through different mutation combinations when compared to S. aureus ATCC 25293. Especially mprF and cls1 showed very high polymorphism in most isolates. Meanwhile, one isolate, MSa5, showed only single mutation in mprF (P314T).

5.
Poult Sci ; 103(2): 103278, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38052127

RESUMO

It has been hypothesized that reducing the bioenergetic costs of gut inflammation as an explanation for the effect of antibiotic growth promoters (AGPs) on animal efficiency, framing some observations but not explaining the increase in growth rate or the prevention of infectious diseases. The host's ability to adapt to alterations in environmental conditions and to maintain health involves managing all physiological interactions that regulate homeostasis. Thus, metabolic pathways are vital in regulating physiological health as the energetic demands of the host guides most biological functions. Mitochondria are not only the metabolic heart of the cell because of their role in energy metabolism and oxidative phosphorylation, but also a central hub of signal transduction pathways that receive messages about the health and nutritional states of cells and tissues. In response, mitochondria direct cellular and tissue physiological alterations throughout the host. The endosymbiotic theory suggests that mitochondria evolved from prokaryotes, emphasizing the idea that these organelles can be affected by some antibiotics. Indeed, therapeutic levels of several antibiotics can be toxic to mitochondria, but subtherapeutic levels may improve mitochondrial function and defense mechanisms by inducing an adaptive response of the cell, resulting in mitokine production which coordinates an array of adaptive responses of the host to the stressor(s). This adaptive stress response is also observed in several bacteria species, suggesting that this protective mechanism has been preserved during evolution. Concordantly, gut microbiome modulation by subinhibitory concentration of AGPs could be the result of direct stimulation rather than inhibition of determined microbial species. In eukaryotes, these adaptive responses of the mitochondria to internal and external environmental conditions, can promote growth rate of the organism as an evolutionary strategy to overcome potential negative conditions. We hypothesize that direct and indirect subtherapeutic AGP regulation of mitochondria functional output can regulate homeostatic control mechanisms in a manner similar to those involved with disease tolerance.


Assuntos
Microbioma Gastrointestinal , Aves Domésticas , Animais , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Galinhas , Mitocôndrias/metabolismo
6.
Eur J Pharm Biopharm ; 191: 158-165, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37536578

RESUMO

The development of biofilms on different surfaces continues to be a major public health problem. The antimicrobial resistance and the difficulty of finding drugs capable of combating these established biofilms generates the urgent need to find compounds that prevent cells from settling and establishing of these complex communities of microorganisms. Zwitterionic modification of nanomaterials allows the formation of a hydration layer, and this highly hydrophilic surface provides antifouling properties as well as a good biocompatibility by preventing non-specific interactions. Thus, they are appropriate candidates to prevent microbial adhesion to different surfaces and, in consequence, avoid biofilm formation. For this reason, we have incorporated zwitterionic moieties in multivalent systems, as are carbosilane dendrimers. Characterization of these systems was performed using nuclear magnetic resonance and mass spectrometry. It has been analysed if the new molecules have capacity to inhibit the biofilm formation in Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that they were more effective against S. aureus, observing a biofilm reduction of 81.5% treating with 32 mg/L of G2SiZWsf dendrimer and by 72.5% using 32 mg/L of the G3SiZWsf dendrimer. Finally, the absence of cytotoxicity was verified by haemolysis and cytotoxicity studies in human cells lines.


Assuntos
Dendrímeros , Eucariotos , Humanos , Dendrímeros/farmacologia , Staphylococcus aureus , Candida albicans , Biofilmes , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
7.
Pharmaceutics ; 14(8)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-36015230

RESUMO

In the last decade, Candida glabrata has become an important emerging opportunistic pathogen not only because of the increase in nosocomial infections frequency but also because of its ability to form biofilms and its innate resistance to commercial antifungals. These characteristics make this pathogen a major problem in hospital settings, including problems regarding equipment, and in immunosuppressed patients, who are at high risk for candidemia. Therefore, there is an urgent need for the development of and search for new antifungal drugs. In this study, the efficacy of two dendritic wedges with 4-phenyl butyric acid (PBA) at the focal point and cationic charges on the surface ArCO2G2(SNMe3I)4 (1) and ArCO2G3(SNMe3I)8 (2) was studied against C. glabrata strain to inhibit the formation of biofilms and eliminate established biofilm. For this, MBIC (minimum biofilm inhibitory concentration), MBDC (minimum biofilm damaging concentrations), as well as MFCB (minimum fungicidal concentration in biofilm) and MBEC (minimum biofilm eradicating concentration) were determined. In addition, different combinations of dendrons and amphotericin B were tested to study possible synergistic effects. On the other hand, cytotoxicity studies were performed. C. glabrata cells and biofilm structure were visualized by confocal microscopy. ArCO2G2(SNMe3I)4 (1) and ArCO2G3(SNMe3I)8 (2) dendrons showed both an MBIC of 8 mg/L and a MBDC of 32 mg/L and 64 mg/L, respectively. These dendrons managed to eradicate the entirety of an established biofilm. In combination with the antifungal amphotericin, it was possible to prevent the generation of biofilms and eradicate established biofilms at lower concentrations than those required individually for each compound at these conditions.

8.
Int J Mol Sci ; 23(3)2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35163794

RESUMO

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin-CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.


Assuntos
Antibacterianos/farmacologia , Endopeptidases/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/crescimento & desenvolvimento , Silanos/farmacologia , Antibacterianos/química , Bacteriófagos/metabolismo , Biofilmes/efeitos dos fármacos , Dendrímeros , Composição de Medicamentos , Sinergismo Farmacológico , Interferometria , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Microscopia de Fluorescência , Plâncton/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Silanos/química
9.
J Fungi (Basel) ; 7(7)2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34356953

RESUMO

Candida albicans is a human pathogen of significant clinical relevance. This pathogen is resistant to different drugs, and most clinical antifungals are not effective against the prevention and treatment of C. albicans infections. As with other microorganisms, it can produce biofilms that serve as a barrier against antifungal agents and other substances, contributing to infection in humans and environmental tolerance of this microorganism. Thus, resistances and biofilm formation make treatment difficult. In addition, the complete eradication of biofilms in implants, catheters and other medical devices, is challenging and necessary to prevent relapses of candidemia. Therefore, it is a priority to find new molecules or combinations of compounds with anti-Candida biofilm activity. Due to the difficulty of treating and removing biofilms, the aim of this study was to evaluate the in vitro ability of different generation of cationic carbosilane dendrons derived from 4-phenylbutyric acid, ArCO2Gn(SNMe3I)m, to eradicate C. albicans biofilms. Here, we assessed the antifungal activity of the second generation dendron ArCO2G2(SNMe3I)4 against C. albicans cells and established biofilms since it managed to seriously damage the membrane. In addition, the combinations of the second generation dendron with AgNO3 or EDTA eradicated the viability of biofilm cells. Alterations were observed by scanning electron microscopy and cytotoxicity was assessed on HeLa cells. Our data suggest that the dendritic compound ArCO2G2(SNMe3I)4 could represent an alternative to control the infections caused by this pathogen.

10.
Polymers (Basel) ; 13(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209475

RESUMO

Antibiotic resistance and biofilm-related infections, persistent in conventional antimicrobial treatment, are continuously increasing and represent a major health problem worldwide. Therefore, the development of new effective treatments to prevent and treat biofilm-related infections represents a crucial challenge. Unfortunately, the extensive use of antibiotics has led to an increase of resistant bacteria with the subsequent loss of effectivity of commercial antibiotics, mainly due to antibiotic resistance and the ability of some bacteria to form microbial communities in biotic or abiotic surfaces (biofilms). In some cases, these biofilms are resistant to high concentrations of antibiotics that lead to treatment failure and recurrence of the associated infections. In the fight against microbial resistance, the combination of traditional antibiotics with new compounds (combination therapy) is an alternative that is becoming more extensive in the medical field. In this work, we studied the cooperative effects between levofloxacin, an approved antibiotic, and peptides or cationic dendritic molecules, compounds that are emerging as a feasible solution to overcome the problem of microbial resistance caused by pathogenic biofilms. We studied a new therapeutic approach that involves the use of levofloxacin in combination with a cationic carbosilane dendron, called MalG2(SNHMe2Cl)4, or a synthetic cell-penetrating peptide, called gH625, conjugated to the aforementioned dendron. To carry out the study, we used two combinations (1) levofloxacin/dendron and (2) levofloxacin/dendron-peptide nanoconjugate. The results showed the synergistic effect of the combination therapy to treat Staphylococcus aureus biofilms. In addition, we generated a fluorescein labeled peptide that allowed us to observe the conjugate (dendron-peptide) localization throughout the bacterial biofilm by confocal laser scanning microscopy.

11.
Pharmaceutics ; 12(10)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992733

RESUMO

Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candidaalbicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16-32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.

12.
Int Immunopharmacol ; 81: 106269, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32036273

RESUMO

IgY-technology (the production and extraction of specific IgY antibodies from egg yolk) is an innovative method to produce antibodies for therapy and prophylaxis. Advantages of IgY over other antibodies comprise its cost-effective extraction, the minimization of animal harm and distress, and its reduced reactivity with mammalian factors. Many research groups have demonstrated that IgY is active against several pathogens or conditions, a fact that may support the design of novel, safe and effective health products. This review provides a comprehensive analysis of IgY-based biologicals for human medicine, including patent applications and clinical trials during the period 2010-2018, and addresses how IgY-technology can lead to innovation in the production of biologicals for the treatment and prophylaxis of a wide range of infectious and non-communicable diseases.


Assuntos
Anticorpos/uso terapêutico , Produtos Biológicos/uso terapêutico , Imunoglobulinas/metabolismo , Animais , Galinhas , Ensaios Clínicos como Assunto , Gema de Ovo/imunologia , Humanos , Patentes como Assunto
13.
J Agric Food Chem ; 68(10): 2836-2848, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31117489

RESUMO

Wood extracts are one of the most important natural sources of industrially obtained tannins. Their use in the food industry could be one of the biggest (most important) recent innovations in food science as a result of their multiple (many) possible applications. The use of tannin wood extracts (TWEs) as additives directly added in foods or in their packaging meets an ever-increasing consumer demand for innovative approaches to sustainability. The latest research is focusing on new ways to include them directly in food, to take advantage of their specific actions to prevent individual pathological conditions. The present review begins with the biology of TWEs and then explores their chemistry, specific sensorial properties, and current application in food production. Moreover, this review is intended to cover recent studies dealing with the potential use of TWEs as a starting point for novel food ingredients.


Assuntos
Ingredientes de Alimentos/análise , Extratos Vegetais/análise , Taninos/análise , Madeira/química , Indústria Alimentícia , Humanos
14.
Microorganisms ; 7(10)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547108

RESUMO

Gut microbiota and its relationship to animal health and productivity in commercial broiler chickens has been difficult to establish due to high variability between flocks, which derives from plenty of environmental, nutritional, and host factors that influence the load of commensal and pathogenic microbes surrounding birds during their growth cycle in the farms. Chicken gut microbiota plays a key role in the maintenance of intestinal health through its ability to modulate host physiological functions required to maintain intestinal homeostasis, mainly through competitive exclusion of detrimental microorganisms and pathogens, preventing colonization and therefore decreasing the expense of energy that birds normally invest in keeping the immune system active against these pathogens. Therefore, a "healthy" intestinal microbiota implies energy saving for the host which translates into an improvement in productive performance of the birds. This review compiles information about the main factors that shape the process of gut microbiota acquisition and maturation, their interactions with chicken immune homeostasis, and the outcome of these interactions on intestinal health and productivity.

15.
Hepatology ; 70(2): 650-665, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30155948

RESUMO

Liver ischemia and reperfusion injury (IRI) remains a serious clinical problem affecting liver transplantation outcomes. IRI causes up to 10% of early organ failure and predisposes to chronic rejection. Cyclooxygenase-2 (COX-2) is involved in different liver diseases, but the significance of COX-2 in IRI is a matter of controversy. This study was designed to elucidate the role of COX-2 induction in hepatocytes against liver IRI. In the present work, hepatocyte-specific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were subjected to IRI. hCOX-2-Tg mice exhibited lower grades of necrosis and inflammation than Wt mice, in part by reduced hepatic recruitment and infiltration of neutrophils, with a concomitant decrease in serum levels of proinflammatory cytokines. Moreover, hCOX-2-Tg mice showed a significant attenuation of the IRI-induced increase in oxidative stress and hepatic apoptosis, an increase in autophagic flux, and a decrease in endoplasmic reticulum stress compared to Wt mice. Interestingly, ischemic preconditioning of Wt mice resembles the beneficial effects observed in hCOX-2-Tg mice against IRI due to a preconditioning-derived increase in endogenous COX-2, which is mainly localized in hepatocytes. Furthermore, measurement of prostaglandin E2 (PGE2 ) levels in plasma from patients who underwent liver transplantation revealed a significantly positive correlation of PGE2 levels and graft function and an inverse correlation with the time of ischemia. Conclusion: These data support the view of a protective effect of hepatic COX-2 induction and the consequent rise of derived prostaglandins against IRI.


Assuntos
Ciclo-Oxigenase 2/biossíntese , Hepatócitos/enzimologia , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/etiologia , Animais , Ciclo-Oxigenase 2/fisiologia , Masculino , Camundongos , Camundongos Transgênicos
16.
Toxicon ; 148: 149-154, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29698757

RESUMO

Shiga toxin-producing Escherichia coli (STEC) have been implicated as the cause of enterotoxemias, such as hemolytic uremic syndrome in humans and edema disease (ED) of pigs. Stx1 and Stx2 are the most common types found in association with illness, but only Stx2e is associated with disease in the animal host. Porcine edema disease is a serious affection which can lead to dead causing great losses of weaned piglets. Stx2e is the most frequent Stx variant found in porcine feces and is considered the key virulence factor involved in the pathogenesis of porcine edema disease. Stx2e binds with higher affinity to Gb4 receptor than to Gb3 which could be due to amino acid changes in B subunit. Moreover, this subtype also binds to Forssman glycosphingolipids conferring upon Stx2e a unique promiscuous recognition feature. Manifestations of edema disease are caused by systemic effects of Stx2e with no significant morphologic changes in enterocytes. Endothelial cell necrosis in the brain is an early event in the pathogenesis of ED caused by Stx2e-producing STEC strains. Further studies are needed to generate techniques and tools which allow to understand the circulation and ecology of STEC strains in pigs even in resistant animals for diagnostic and epidemiological purposes.


Assuntos
Infecções por Escherichia coli/veterinária , Toxina Shiga II/toxicidade , Escherichia coli Shiga Toxigênica/patogenicidade , Doenças dos Suínos/microbiologia , Animais , Fezes/química , Globosídeos/metabolismo , Toxina Shiga II/química , Suínos , Virulência/genética
17.
Microb Drug Resist ; 24(7): 1031-1039, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29267134

RESUMO

Candida sp. are found as part of the commensal flora in humans but can cause invasive candidiasis in patients with severe underlying disease, especially cancer patients. These patients are frequently subjected to nonsurgical anticancer treatments such as ionizing radiation and anticancer drugs, which kill proliferating human cells by damaging DNA but also affect the microbiota of the patient. C. tropicalis, an emerging fungal pathogen, is associated with high mortality rates of cancer patients especially in tropical regions. In this study, we have investigated the in vitro susceptibility of 38 C. tropicalis clinical isolates from several Mexican hospitals to chronic treatments with several DNA damaging agents, including oxidizing compounds and anticancer drugs. C. tropicalis isolates displayed a high variability in their susceptibility to hydrogen peroxide (H2O2) while showing a high susceptibility to bleomycin (BLM), an anticancer drug that causes double-strand breaks in DNA. This contrasted with the moderate-to-high resistance exhibited by several C. albicans laboratory strains. At least for the C. tropicalis reference strain MYA3404, this susceptibility was hardly modified by the presence of serum. Our results open the possibility of using susceptibility to BLM to differentiate between C. tropicalis and C. albicans; however, analysis of a larger number of isolates is required. The use of BLM for prevention of C. tropicalis infections in neutropenic patients with cancer should be also evaluated. Finally, the variable susceptibility to H2O2 might be due to allelic variation of the histone acetyl-transferase complex which modulates the induction kinetics of H2O2-induced genes in C. tropicalis.


Assuntos
Antifúngicos/farmacologia , Bleomicina/farmacologia , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/isolamento & purificação , Peróxido de Hidrogênio/farmacologia , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Proliferação de Células/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana
18.
Rev. esp. quimioter ; 30(6): 391-396, dic. 2017. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-169391

RESUMO

Daptomycin is a cyclic lipopeptide active against multidrug-resistant Gram-positives, including methicillinresistant Staphylococcus aureus (MRSA) and S. aureus with reduced susceptibility to vancomycin. It is 4-8 fold as active as vancomycin against methicillin-susceptible S. aureus (MSSA) and MRSA, and retains most of this activity against S. aureus with reduced susceptibility to vancomycin. The mechanism of action of daptomycin is not fully understood. Daptomycin binds to the bacterial cytoplasmic membrane, leading to depolarization due to the loss of potassium ions from the cytoplasm. Daptomycin non-susceptibility is unusual in the clinical setting. Different mechanisms have been proposed to explain daptomycin-resistance, most of them associated to changes in composition, charge and fluidity of the cell wall. The mprF mutations, which lead to an increase in the lysyl-phosphatidyl glycerol production, and rpoB and rpoC mutations (rpo genes encode for bacterial RNA polymerase subunits) have been proposed as associated to daptomycinresistance, but a number of mutations in other genes ( walK, cls, ggrA…) have been proposed (AU)


Daptomicina es un lipopéptido cíclico, activo frente a microorganismos grampositivos multirresistentes, incluyendo Staphylococcus aureus resistente a meticilina (SARM) y S. aureus con sensibilidad reducida a vancomicina. Es 4-8 veces más activa que vancomicina frente a S. aureus sensible a meticilina (SASM) y SARM, y mantiene prácticamente la misma actividad frente a S. aureus con sensibilidad reducida a vancomicina. El mecanismo de acción de daptomicina no está completamente explicado. Daptomicina se une a la membrana citoplasmática bacteriana y da lugar a su despolarización, como consecuencia de la pérdida de iones potasio. La resistencia a daptomicina es todavía infrecuente en el ámbito clínico. Se han propuesto diversos mecanismos de resistencia, en su mayor parte asociados a cambios en la composición, carga y fluidez de la membrana celular. Se ha propuesto la asociación de la resistencia a daptomicina con mutaciones en los genes mprF, que dan lugar a un aumento en la producción de lisil-fosfatidil-glicerol, a mutaciones en rpoB y rpoC (los genes rpo codifican diferentes subunidades de la ARN polimerasa bacteriana) pero también a mutaciones en otro numeroso grupo de genes (walK, cls, ggrA, etc.) (AU)


Assuntos
Humanos , Daptomicina/farmacocinética , Infecções Estafilocócicas/tratamento farmacológico , Resistência Microbiana a Medicamentos , Staphylococcus aureus/patogenicidade , Testes de Sensibilidade Microbiana
19.
Medicina (B Aires) ; 77(3): 201-206, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28643677

RESUMO

Watercress (Nasturtium officinale, Cruciferae; W. Aiton) is a vegetable widely consumed in our country, with nutritional and potentially chemopreventive properties. Previous reports from our laboratory demonstrated the protective effect of watercress juice against DNA damage induced by cyclophosphamide in vivo. In this study, we evaluated the in vivo effect of cress plant on the oxidative stress in mice. Animals were treated by gavage with different doses of watercress juice (0.5 and 1g/kg body weight) for 15 consecutive days before intraperitoneal injection of cyclophosphamide (100 mg/kg body weight). After 24 h, mice were killed by cervical dislocation. The effect of watercress was investigated by assessing the following oxidative stress biomarkers: catalase activity, superoxide dismutase activity, lipid peroxidation, and glutathione balance. Intake of watercress prior to cyclophosphamide administration enhanced superoxide dismutase activity in erythrocytes with no effect on catalase activity. In bone marrow and liver tissues, watercress juice counteracted the effect of cyclophosphamide. Glutathione balance rose by watercress supplementation and lipid oxidation diminished in all matrixes when compared to the respective control groups. Our results support the role of watercress as a diet component with promising properties to be used as health promoter or protective agent against oxidative damage.


Assuntos
Antioxidantes/farmacologia , Ciclofosfamida/farmacologia , Nasturtium/química , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/isolamento & purificação , Dano ao DNA , Glutationa , Peroxidação de Lipídeos , Camundongos , Folhas de Planta
20.
Medicina (B.Aires) ; 77(3): 201-206, jun. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-894458

RESUMO

Watercress (Nasturtium officinale, Cruciferae; W. Aiton) is a vegetable widely consumed in our country, with nutritional and potentially chemopreventive properties. Previous reports from our laboratory demonstrated the protective effect of watercress juice against DNA damage induced by cyclophosphamide in vivo. In this study, we evaluated the in vivo effect of cress plant on the oxidative stress in mice. Animals were treated by gavage with different doses of watercress juice (0.5 and 1g/kg body weight) for 15 consecutive days before intraperitoneal injection of cyclophosphamide (100 mg/kg body weight). After 24 h, mice were killed by cervical dislocation. The effect of watercress was investigated by assessing the following oxidative stress biomarkers: catalase activity, superoxide dismutase activity, lipid peroxidation, and glutathione balance. Intake of watercress prior to cyclophosphamide administration enhanced superoxide dismutase activity in erythrocytes with no effect on catalase activity. In bone marrow and liver tissues, watercress juice counteracted the effect of cyclophosphamide. Glutathione balance rose by watercress supplementation and lipid oxidation diminished in all matrixes when compared to the respective control groups. Our results support the role of watercress as a diet component with promising properties to be used as health promoter or protective agent against oxidative damage.


El berro (Nasturtium officinale, crucíferas; W. Aiton) es una hortaliza ampliamente consumida en nuestro país, con valor nutricional y propiedades potencialmente quimiopreventivas. En trabajos previos demostramos que el jugo de berro tiene efecto protector in vivo contra el daño del ADN inducido por ciclofosfamida en tejidos del ratón. En el presente trabajo evaluamos, también in vivo, los efectos del jugo sobre el estrés oxidativo en diferentes tejidos del ratón. Los siguientes biomarcadores fueron investigados: actividad de superóxido dismutasa, actividad de catalasa, peroxidación lipídica y balance de glutatión. Los animales fueron tratados con diferentes dosis de jugo (0.5 y 1 g/kg de peso corporal) por alimentación forzada durante 15 días consecutivos antes de la inyección intraperitoneal con ciclofosfamida (100 mg/kg). La ingesta de berro antes de la administración de ciclofosfamida mejoró la actividad de superóxido dismutasa en los eritrocitos sin efecto sobre la actividad de la catalasa. En médula ósea e hígado, el jugo de berro contrarrestó el efecto deletéreo de la ciclofosfamida. En todas las matrices, el balance de glutatión fue mayor y la oxidación de lípidos menor que los valores encontrados en los grupos control. Nuestros resultados demuestran que el berro es un componente de la dieta con propiedades prometedoras como promotor de la salud o como agente protector contra el daño oxidativo.


Assuntos
Animais , Coelhos , Estresse Oxidativo/efeitos dos fármacos , Ciclofosfamida/farmacologia , Nasturtium/química , Antioxidantes/farmacologia , Dano ao DNA , Peroxidação de Lipídeos , Folhas de Planta , Glutationa , Antioxidantes/isolamento & purificação
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