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1.
Anaerobe ; 82: 102767, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37482285

RESUMO

Members of the Actinomyces genus and Actinomyces-like organisms (ALOs; namely Actinotignum, Arcanobacterium, Schaalia and Varibaculum) are Gram-positive, non-spore-forming rods that are commensal members of the human oral cavity, gastrointestinal tract, female genital tract and skin microbiota. Cervicofacial actinomycosis or "lumpy jaw syndrome" - the chronic, suppurative granulomatous disease caused by Actinomyces spp. And ALOs - is characterized by an initially slow and unspecific disease-presentation, which often mimics other pathologies, followed by the formation of painful abscesses and severe tissue destruction. Actinomycosis has been described as a rare disease, however, reliable epidemiological data are lacking. In addition, there is increasing awareness regarding the role of Actinomyces spp. in the development of osteoradionecrosis and medication-related osteonecrosis of the jaw. The aim of this narrative review is to succinctly summarize the current advances regarding the microbiological, clinical, diagnostic and therapeutic aspects of cervicofacial actinomycosis, in addition to the roles of Actinomyces species and ALOs as members of the oral microbiota and in dental biofilm, in other dental infections (caries, root canal infection, periapical infection, periodontitis) and osteonecrosis of the jaw, in the context of recent taxonomic changes affecting the genus. Our paper aims to be a blueprint for dentists, other physicians, microbiologists and researchers regarding the multifaceted field of cervicofacial actinomycosis.


Assuntos
Actinomycetaceae , Actinomicose Cervicofacial , Actinomicose , Osteonecrose , Feminino , Humanos , Actinomyces , Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico , Actinomicose Cervicofacial/diagnóstico , Actinomicose Cervicofacial/tratamento farmacológico , Boca
2.
Molecules ; 28(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37175130

RESUMO

New 2-thioxopyrimidin-4-ones capable of participating in regioselective reactions with functionally diverse hydrazonoyl chlorides towards angular regioisomers, rather than linear ones, were designed and synthesized to form stereoisomeric cis- and trans-hexahydro [1,2,4]triazolo[4,3-a]quinazolin-9-ones to be tested as antitumor candidates. The angular regiochemistry of the products was verified through crystallographic experiments and NMR studies. In addition, the regioselectivity of the reaction was found to be independent of the stereochemistry of the used 2-thioxopyrimidin-4-one. Only compound 4c demonstrated satisfactory growth inhibition against all the cancer cells used among all the produced drugs.

3.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 33-41, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35809304

RESUMO

Excessive use of refined flour, solid fats, and sugar in preparing baked products are considered to be unhealthy and is intricately linked with the development of lifestyle diseases. Replacing refined flour with whole wheat flour and solid fats with cold-pressed oil serves as an alternate option. The study was aimed at evaluating the physicochemical properties, nutrient composition, sensory attributes, and shelf life of cupcakes enriched using pomegranate seed oil (PSO). Vanilla and chocolate cupcake variants were prepared using 25 and 50% of PSO. A sensory panel consisting of 30 semi-trained participants was selected for evaluating the formulated products using a five-point hedonic scale. Nutrient content was estimated using standard techniques. The stability of the formulated product was determined by evaluating the physicochemical traits and microbial growth on the 0th, 4th, and 7th day. Mean scores of the sensorial analysis showed that the incorporation of PSO in cupcakes was highly accepted by the panel members. Chocolate cupcake containing 50% of PSO was found to be the most preferred product (3.53±0.94), followed by vanilla cupcake containing 25% of PSO (3.4±0.62). The moisture, protein, and fat content of chocolate cupcakes containing 25% of PSO were high. Cupcakes prepared with PSO can be stored for four days at room temperature. GC-MS analysis showed the presence of punicic acid, oleic acid, tocopherols, campesterol, sitosterols, stigmasterol, and α-tocopheryl acetate as pre-dominant fatty acid in unheated and heated PSO. In conclusion, cupcakes prepared using PSO showed acceptable physicochemical qualities and sensory properties which indicated its successful consumption by people affected with metabolic disorders.


Assuntos
Análise de Alimentos , Qualidade dos Alimentos , Óleos de Plantas , Punica granatum , Ácidos Graxos/análise , Ácidos Graxos/química , Microbiologia de Alimentos , Humanos , Óleos de Plantas/química , Punica granatum/química , Sementes , Edulcorantes , Adulto Jovem
4.
Adv Exp Med Biol ; 1323: 35-69, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32596751

RESUMO

Urinary tract infections (UTIs) are some of the most common infections in human medicine worldwide, recognized as an important public health concern to healthcare systems around the globe. In addition, urine specimens are one of the most frequently submitted samples for culture to the clinical microbiology laboratory, exceeding the number of most of the other sample types. The epidemiology, species-distribution and susceptibility-patterns of uropathogens vary greatly in a geographical and time-dependent manner and it also strongly correlated with the reported patient population studied. Nevertheless, many studies highlight the fact that the etiological agents in UTIs have changed considerably, both in nosocomial and community settings, with a shift towards "less common" microorganisms having more pronounced roles. There is increasing demand for further research to advance diagnostics and treatment options, and to improve care of the patients. The aim of this review paper was to summarize current developments in the global burden of UTI, the diagnostic aspects of these infectious pathologies, the possible etiological agents and their virulence determinants (with a special focus on the members of the Enterobacterales order), current guidelines and quality indicators in the therapy of UTIs and the emergence of multidrug resistance in urinary pathogens.


Assuntos
Antibacterianos , Infecções Urinárias , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas , Humanos , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-34524972

RESUMO

Bacteria can enhance their survival by attaching to inanimate surfaces or tissues, and presenting as multicellular communities encased in a protective extracellular matrix called biofilm. There has been pronounced interest in assessing the relationship between the antibiotic resistant phenotype and biofilm-production in clinically-relevant pathogens. The aim of the present paper was to provide additional experimental results on the topic, testing the biofilm-forming capacity of Escherichia coli isolates using in vitro methods in the context of their antibiotic resistance in the form of a laboratory case study, in addition to provide a comprehensive review of the subject. In our case study, a total of two hundred and fifty (n = 250) E. coli isolates, originating from either clean-catch urine samples (n = 125) or invasive samples (n = 125) were included. The colony morphology of isolates were recorded after 24h, while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm-formation of the isolates was assessed with the crystal violet tube-adherence method. Altogether 57 isolates (22.8%) isolates were multidrug resistant (MDR), 89 isolates (35.6%) produced large colonies (>3 mm), mucoid variant colonies were produced in 131 cases (52.4%), and 108 (43.2%) were positive for biofilm formation. Biofilm-producers were less common among isolates resistant to third-generation cephalosporins and trimethoprim-sulfamethoxazole (P = 0.043 and P = 0.023, respectively). Biofilms facilitate a protective growth strategy in bacteria, ensuring safety against environmental stressors, components of the immune system and noxious chemical agents. Being an integral part of bacterial physiology, biofilm-formation is interdependent with the expression of other virulence factors (especially adhesins) and quorum sensing signal molecules. More research is required to allow for the full understanding of the interplay between the MDR phenotype and biofilm-production, which will facilitate the development of novel therapeutic strategies.

6.
Int J Mol Sci ; 22(24)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34948048

RESUMO

Due to its tensile strength and excellent biocompatibility, titanium (Ti) is commonly used as an implant material in medicine and dentistry. The success of dental implants depends on the formation of a contact between the oxidized surface of Ti implant and the surrounding bone tissue. The adsorption of proteins and peptides to the implant surface allows the bone-forming osteoblast cells to adhere to such modified surfaces. Recently, it has been observed that tetrapeptide KRSR (Lys-Arg-Ser-Arg) functionalization could promote osteoblast adhesion to implant surfaces. This may facilitate the establishment of an efficient bone-to implant contact and improve implant stability during the healing process. GROMACS, a molecular dynamics software package was used to perform a 200 ns simulation of adsorption of the KRSR peptide to the TiO2 (anatase) surface in an aqueous environment. The molecule conformations were mapped with Replica Exchange Molecular Dynamics (REMD) simulations to assess the possible peptide conformations on the anatase surface, and the umbrella sampling method was used to calculate the binding energy of the most common conformation. The simulations have shown that the KRSR peptide migrates and attaches to the surface in a stable position. The dominant amino acid residue interacting with the TiO2 surface was the N-terminal charged lysine (K) residue. REMD indicated that there is a distinct conformation that is taken by the KRSR peptide. In this conformation the surface interacts only with the lysine residue while the ser (S) and arg (R) residues interact with water molecules farther from the surface. The binding free energy of the most common conformation of KRSR peptide to the anatase (100) surface was ΔG = -8.817 kcal/mol. Our result suggests that the N-terminal lysine residue plays an important role in the adhesion of KRSR to the TiO2 surface and may influence the osseointegration of dental implants.


Assuntos
Oligopeptídeos/química , Titânio/química , Modelos Moleculares , Conformação Molecular , Simulação de Dinâmica Molecular
7.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203823

RESUMO

There are two main types of bacterial photosynthesis: oxygenic (cyanobacteria) and anoxygenic (sulfur and non-sulfur phototrophs). Molecular mechanisms of photosynthesis in the phototrophic microorganisms can differ and depend on their location and pigments in the cells. This paper describes bacteria capable of molecular oxidizing hydrogen sulfide, specifically the families Chromatiaceae and Chlorobiaceae, also known as purple and green sulfur bacteria in the process of anoxygenic photosynthesis. Further, it analyzes certain important physiological processes, especially those which are characteristic for these bacterial families. Primarily, the molecular metabolism of sulfur, which oxidizes hydrogen sulfide to elementary molecular sulfur, as well as photosynthetic processes taking place inside of cells are presented. Particular attention is paid to the description of the molecular structure of the photosynthetic apparatus in these two families of phototrophs. Moreover, some of their molecular biotechnological perspectives are discussed.


Assuntos
Chlorobi/genética , Chlorobi/fisiologia , Chromatiaceae/genética , Chromatiaceae/fisiologia , Processos Fototróficos/genética , Anaerobiose , Chlorobi/classificação , Chromatiaceae/classificação , Filogenia , Enxofre/metabolismo
8.
Ideggyogy Sz ; 74(1-2): 17-25, 2021 Jan 30.
Artigo em Húngaro | MEDLINE | ID: mdl-33497059

RESUMO

Brain abscesses are potentially serious, life-threatening diseases that pose a complex diagnostic challenge not only to neurosurgeons but also to clinical microbiologists, neurologists, psychiatrists, infectologists. The etiology of brain abscess is usually polymicrobial, most commonly involving a variety of aerobic and obligate anaerobic bacteria. Epidemiological studies on the anaerobic etiology of brain abscesses are common between the time period of 1960s and 1980s, but today there are very few new publications on the subject. The role of anaerobic bacteria in this disease was presumably underdiagnosed for a very long time, as many laboratories did not have the adequate laboratory capabilities for their cultivation and identification. The purpose of this review is to summarize the available literature on the etiology of obligate anaerobic bacteria in brain abscesses, including their prevalence and current therapeutic recommendations.


Assuntos
Bactérias Anaeróbias , Abscesso Encefálico , Abscesso Encefálico/diagnóstico , Humanos
9.
Bioorg Med Chem ; 28(23): 115798, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038666

RESUMO

Naringenin (1), isolated from Euphorbia pedroi, was previously derivatized yielding compounds 2-13. In this study, aiming at expanding the pool of analogues of the flavanone core towards better multidrug resistance (MDR) reversal agents, alkylation reactions and chemical modification of the carbonyl moiety was performed (15-39). Compounds structures were assigned mainly by 1D and 2D NMR experiments. Compounds 1-39 were assessed as MDR reversers, in human ABCB1-transfected mouse T-lymphoma cells, overexpressing P-glycoprotein (P-gp). The results revealed that O-methylation at C-7, together with the introduction of nitrogen atoms and aromatic moieties at C-4 or C-4', significantly improved the activity, being compounds 27 and 37 the strongest P-gp modulators and much more active than verapamil. In combination assays, synergistic interactions of selected compounds with doxorubicin substantiated the results. While molecular docking suggested that flavanone derivatives act as competitive modulators, molecular dynamics showed that dimethylation promotes binding to a modulator-binding site. Moreover, flavanones may also interact with a vicinal ATP-binding site in both nucleotide-binding domains, hypothesizing an allosteric mode of action.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Flavanonas/química , Nitrogênio/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Sítios de Ligação , Ligação Competitiva , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Euphorbia/química , Euphorbia/metabolismo , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Humanos , Linfoma de Células T/patologia , Camundongos , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
10.
Acta Microbiol Immunol Hung ; 67(3): 148-155, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32223305

RESUMO

Streptococcus suis is an emerging zoonotic human pathogen, which is a causative agent of invasive infections in people who are in close contact with infected pigs or contaminated pork products. It is associated with severe systemic infections, most commonly meningitis and sepsis, which may lead to high rates of morbidity and mortality. Serotype 2 is the most prevalent type in S. suis infections in humans. We have reported a case of a very rapidly proceeding fatal human S. suis infection in a splenectomized, but otherwise immunocompetent patient in Hungary. We would like to highlight the attention for this pathogen for the risk group patients, not only pig breeders, veterinarians, abattoir workers, meat processing and transport workers, butchers and cooks, that those persons who are immunocompromised including those with spleen removed, persons with diabetes mellitus, cancer and alcoholism, are also at greater risk of infection.


Assuntos
Bacteriemia/microbiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Adulto , Animais , Bacteriemia/diagnóstico , DNA Bacteriano , Evolução Fatal , Interações Hospedeiro-Patógeno , Humanos , Hungria , Hospedeiro Imunocomprometido , Masculino , Carne de Porco/microbiologia , RNA Ribossômico 16S , Fatores de Risco , Esplenectomia/efeitos adversos , Streptococcus suis/isolamento & purificação , Suínos
11.
Artigo em Inglês | MEDLINE | ID: mdl-32845853

RESUMO

Implants have been considered the treatment of choice to replace missing teeth, unfortunately, peri-implant disease is still an unresolved issue. Contaminated implants may be decontaminated by physical debridement and chemical disinfectants; however, there is a lack of consensus regarding the ideal techniques/agents to be used for the decontamination. The objective of our study was to compare the decontaminating efficacy of different chemical agents on a titanium surface contaminated with Porphyromonas gingivalis, a typical representative of the bacterial flora associated with peri-implantitis. Commercially pure Ti grade 4 discs with a polished surface were treated with a mouthwash containing chlorhexidine digluconate (0.1%), povidone-iodine (PVP-iodine) solution (10%) or citric acid monohydrate (40%). Qualitative and quantitative assessment of cellular growth and survival were assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). Significant differences in the quantity of P. gingivalis could be observed after 6 days of incubation. A numerical, but not statistically significant (P = 0.066) decrease in the amount of living bacteria was observed in the group treated with the PVP-iodine solution as compared to the control group. The chlorhexidine (CHX)-treated group presented with significantly higher cell counts, as compared to the PVP-iodine-treated group (P = 0.032), while this was not observed compared to the control group and citric acid-treated group. Our results have also been verified by SEM measurements. Our results suggest that for P. gingivalis contamination on a titanium surface in vitro, PVP-iodine is a superior decontaminant, compared to citric acid and chlorhexidine-digulconate solution.

12.
Acta Microbiol Immunol Hung ; 67(4): 209-215, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258795

RESUMO

Infections caused by carbapenem-resistant Enterobacterales (CRE) present an important therapeutic problem, as there are limited number of effective therapeutic alternatives available. In this study, phenotypic and genotypic methods were used to characterize carbapenemase-production and other resistance-determinants (AmpC and ESBL-production, efflux pump-overexpression) in 50 isolates (Klebsiella spp. n = 35, Escherichia coli n = 12 and Enterobacter cloacae complex n = 3) collected at the Albert Szent-Györgyi Clinical Center (University of Szeged) between 2014 and 2017. Minimum inhibitory concentrations of meropenem, sulfamethoxazole/trimethoprim, tigecycline, amikacin, moxifloxacin, colistin and fosfomycin were also determined. 24% of isolates were AmpC-producers, while 30% carried blaCTX-M ESBL-genes. Carbapenemase-genes were detected in 18 (36%) of the tested isolates: in 2 isolates blaNDM, in 6 isolates blaOXA-48-like and in 12 isolates, blaVIM was detected by PCR. The species-distribution for isolates positive for carbapenemase-genes was the following: Klebsiella pneumoniae n = 11, Klebsiella oxytoca n = 1, E. coli n = 5, E. cloacae complex n = 1. Efflux pump-overexpression based on the PAßN-screening agar was shown in n = 3 of the tested strains. In nine isolates (18%), carbapenemase and ESBL-genes were detected simultaneously. Highest levels of resistance were noted for fosfomycin (74%) and moxifloxacin (70%), while all isolates were susceptible to colistin. Among applied phenotypic tests in this study the modified carbapenem inactivation method (mCIM) proved to be the most accurate one compared to that of PCR results.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , beta-Lactamases/biossíntese , beta-Lactamases/genética , Proteínas de Bactérias/classificação , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Proteínas de Escherichia coli/biossíntese , Proteínas de Escherichia coli/genética , Humanos , Hungria , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Testes de Sensibilidade Microbiana , beta-Lactamases/classificação
13.
Anaerobe ; 63: 102200, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32247001

RESUMO

Anaerobic bacteremia (AB) is usually detected in about 0.5-13% of positive blood cultures. The aim of this study was to determine prevalence of anaerobic bacteremia over a 5-year period (2013-2017), to identify current trends at our University Hospital and to compare the results to those in a similar study (2005-2009) in the same region. During the study period, an average of 23,274 ±â€¯2,756 blood cultures were received per year. Out of the positive blood cultures, 3.3-3.6% (n = 423) yielded anaerobic bacteria, representing 3.5-3.8 anaerobic isolates/1000 blood culture bottles (including both aerobic and anaerobic bottles) per year for hospitalized patients. Mean age of affected patients was 70-73 years (range: 18-102 years) with a male-to-female ratio: 0.60. Most isolated anaerobes were Cutibacterium spp. (54.0 ±â€¯8.5%; n = 247), while among anaerobes other than Cutibacterium spp., Bacteroides and Parabacteroides and Clostridium spp. were the most prevalent. Blood culture time-to-positivity (TTP) for clinically relevant bacteria was 31.4 ±â€¯23.4 h, while for Cutibacterium spp., TTP values were 112.9 ±â€¯37.2 h (p < 0.0001). In conclusion, the prevalence of anaerobic bacteremia should be determined on institutional basis.


Assuntos
Bactérias Anaeróbias/isolamento & purificação , Sangue/microbiologia , Sepse/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteroides/isolamento & purificação , Bacteroidetes/isolamento & purificação , Hemocultura/métodos , Clostridium/isolamento & purificação , Feminino , Hospitais Universitários , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Propionibacteriaceae/isolamento & purificação , Estudos Retrospectivos , Sepse/epidemiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto Jovem
14.
Medicina (Kaunas) ; 56(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143077

RESUMO

Pathologies of the genito-urinary tract are responsible for a considerable disease burden worldwide, leading to significant losses of income, lost working days, increased expenditures for national healthcare systems, and decreased quality of life (QoL) in the affected patients. Among these diseases, infections and malignancies in this anatomical region are some of the most important illnesses in human medicine; nevertheless, benign prostate hyperplasia (BPH), erectile dysfunction, hypospadias, urinary incontinence, and vesicoureteral reflux are also relevant disorders affecting millions. The publication of various microbiological and clinical studies in urology from different geographical regions has important ramifications from the standpoint of epidemiology: on one hand, reported data may influence the development of therapeutic guidelines for urinary tract infections (UTIs) (empiric antibiotic-therapy) and malignancies (including classical cytotoxic drug protocols and next-generation anticancer therapies) both locally and internationally; on the other hand, the relevant stakeholders and government representatives often base their decisions on published evidence. Therefore, novel studies in the field of urology are strongly encouraged to maintain and improve the high standard of patient care internationally and to ensure continuous information supply for international datasets on the causative agents of UTIs and cancer registries. The present Editorial aims to highlight some relevant studies published from the field of urology in Medicina over the last several years.


Assuntos
Hiperplasia Prostática , Incontinência Urinária , Infecções Urinárias , Urologia , Humanos , Masculino , Qualidade de Vida , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia
15.
Anaerobe ; 59: 112-114, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228670

RESUMO

Diagnostic laboratories are urged to take advantage of novel technological advancements to provide standardized and high-throughput information for clinicians; however, total laboratory automation (TLA) has only recently been introduced in clinical microbiology in the last 10-12 years. The introduction of total laboratory automation comes with certain advantages and drawbacks that need to be assessed before the introduction of such systems in the diagnostic workflow that includes the detection of anaerobic bacteria. For several reasons, there is yet to be a manufacturer to fully address the issue of anaerobes in the setting of laboratory automation; the aim of the present paper is to address some of the issues associated with anaerobes in lab automation.


Assuntos
Automação Laboratorial/métodos , Bactérias Anaeróbias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Técnicas Bacteriológicas/métodos , Técnicas de Laboratório Clínico/métodos , Bactérias Anaeróbias/classificação , Infecções Bacterianas/microbiologia , Humanos
16.
Molecules ; 24(5)2019 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-30832456

RESUMO

The emergence and spread of antibiotic-resistant pathogens is a major public health issue, which requires global action of an intersectoral nature. Multidrug-resistant (MDR) pathogens-especially "ESKAPE" bacteria-can withstand lethal doses of antibiotics with various chemical structures and mechanisms of action. Pharmaceutical companies are increasingly turning away from participating in the development of new antibiotics, due to the regulatory environment and the financial risks. There is an urgent need for innovation in antibiotic research, as classical discovery platforms (e.g., mining soil Streptomycetes) are no longer viable options. In addition to discovery platforms, a concept of an ideal antibiotic should be postulated, to act as a blueprint for future drugs, and to aid researchers, pharmaceutical companies, and relevant stakeholders in selecting lead compounds. Based on 150 references, the aim of this review is to summarize current advances regarding the challenges of antibiotic drug discovery and the specific attributes of an ideal antibacterial drug (a prodrug or generally reactive compound with no specific target, broad-spectrum antibacterial activity, adequate penetration through the Gram-negative cell wall, activity in biofilms and in hard-to-treat infections, accumulation in macrophages, availability for oral administration, and for use in sensitive patient groups).


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Desenho de Fármacos , Descoberta de Drogas/tendências , Antibacterianos/efeitos adversos , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla , Humanos , Streptomycetaceae/efeitos dos fármacos , Streptomycetaceae/patogenicidade
17.
Molecules ; 24(2)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669343

RESUMO

Malignant diseases present a serious public health burden and their treatment with traditional chemotherapy cannot be considered an all-round solution, due to toxic side effects. Selenium compounds (Se-compounds) have received substantial attention in medicinal chemistry, especially in experimental chemotherapy, both as cytotoxic agents and adjuvants in chemotherapy. A checkerboard microplate method was applied to study the drug interactions of Se-compounds and clinically relevant chemotherapeutic drugs against the multidrug-resistant (MDR) subtype of mouse t-lymphoma cells overexpressing the ABCB1 transporter. Se-compounds showed synergistic interactions with chemotherapeutic agents targeting the topoisomerase enzymes or the microtubule apparatus. The ketone-containing selenoesters showed synergism at lower concentrations (1.25 µM). Most of the tested compounds interacted antagonistically with alkylating agents and verapamil. A thiophene-containing Se-compound showed synergism with all tested drugs, except cisplatin. While the exact mechanism of drug interactions is yet unknown, the potency of the selenocompounds as efflux pump inhibitors or the potentiation of their efficacy as reactive oxygen species modulators may play a role in their complementary activity against the tested MDR lymphoma cell line.


Assuntos
Adjuvantes Farmacêuticos/farmacologia , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Adjuvantes Farmacêuticos/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Interações Medicamentosas , Camundongos , Estrutura Molecular , Compostos Organosselênicos/química
18.
Molecules ; 24(23)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31771095

RESUMO

Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications.


Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Antivirais/síntese química , Anidridos Ftálicos/química , Compostos de Selênio/síntese química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Chlorocebus aethiops , Herpesvirus Humano 2/efeitos dos fármacos , Estrutura Molecular , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/fisiologia , Compostos de Selênio/química , Compostos de Selênio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Células Vero
19.
Medicina (Kaunas) ; 55(6)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216725

RESUMO

Background and objectives: Urinary tract infections (UTIs) are the third most common infections in humans, representing a significant factor of morbidity, both among outpatients and inpatients. The pathogenic role of Citrobacter, Enterobacter, and Serratia species (CES bacteria) has been described in UTIs. CES bacteria present a therapeutic challenge due to the various intrinsic and acquired resistance mechanisms they possess. Materials and Methods: The aim of this study was to assess and compare the resistance trends and epidemiology of CES pathogens in UTIs (RECESUTI) in inpatients and outpatients during a 10-year study period. To evaluate the resistance trends of isolated strains, several antibiotics were chosen as indicator drugs based on local utilization data. 578 CES isolates were obtained from inpatients and 554 from outpatients, representing 2.57 ± 0.41% of all positive urine samples for outpatients and 3.02 ± 0.40% for inpatients. E. cloacae was the most prevalent species. Results: The ratio of resistant strains to most of the indicator drugs was higher in the inpatient group and lower in the second half of the study period. ESBL-producing isolates were detected in 0-9.75% from outpatient and 0-29.09% from inpatient samples. Conclusions: Resistance developments of CES bacteria, coupled with their intrinsic non-susceptibility to several antibiotics, severely limits the number of therapeutic alternatives, especially for outpatients.


Assuntos
Citrobacter/patogenicidade , Enterobacter/patogenicidade , Serratia/patogenicidade , Infecções Urinárias/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Hungria/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Inquéritos e Questionários , Infecções Urinárias/epidemiologia , Infecções Urinárias/fisiopatologia
20.
Medicina (Kaunas) ; 55(7)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324035

RESUMO

Background and Objective: Urinary tract infections (UTIs) are common in human medicine, affecting large patient populations worldwide. The principal cause of UTIs is uropathogenic Escherichia coli (UPEC) and Klebsiella, both in community and nosocomial settings. The assessment of local data on prevalence and resistance is essential to evaluate trends over time and to reflect on the national situation, compared to international data, using the methods of analytical epidemiology. Materials and Methods: The aim of this study was to assess resistance trends and epidemiology of UTIs caused by E. coli and Klebsiella species in inpatients and outpatients at a tertiary-care hospital in Hungary, using microbiological data. To evaluate resistance trends, several antibiotics were chosen as indicator drugs, based on local utilization data. Results: E. coli was the most prevalent isolate, representing 56.75 ± 4.86% for outpatients and 42.29 ± 2.94% for inpatients. For E. coli, the ratio of resistant strains for several antibiotics was significantly higher in the inpatient group, while in Klebsiella, similar trends were only observed for gentamicin. Extended-spectrum ß-lactamase (ESBL)-producing isolates were detected in 4.33-9.15% and 23.22-34.22% from outpatient, 8.85-38.97% and 10.89-36.06% from inpatient samples for E. coli and Klebsiella, respectively. Conclusions: Resistance developments in common UTI pathogens (especially to fosfomycin, sulfamethoxazole-trimethoprim, fluoroquinolones, and 3rd generation cephalosporins), seriously curb therapeutic options, especially in outpatient settings.


Assuntos
Farmacorresistência Bacteriana , Infecções Urinárias/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Feminino , Humanos , Hungria/epidemiologia , Lactente , Klebsiella/efeitos dos fármacos , Klebsiella/patogenicidade , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Prevalência , Estudos Retrospectivos , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos , Infecções Urinárias/epidemiologia , beta-Lactamases/uso terapêutico
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