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1.
Int J Mol Sci ; 24(11)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37298471

RESUMO

This review examines the existing knowledge about Ru(II)/(III) ion complexes with a potential application in medicine or pharmacy, which may offer greater potential in cancer chemotherapy than Pt(II) complexes, which are known to cause many side effects. Hence, much attention has been paid to research on cancer cell lines and clinical trials have been undertaken on ruthenium complexes. In addition to their antitumor activity, ruthenium complexes are under evaluation for other diseases, such as type 2 diabetes, Alzheimer's disease and HIV. Attempts are also being made to evaluate ruthenium complexes as potential photosensitizers with polypyridine ligands for use in cancer chemotherapy. The review also briefly examines theoretical approaches to studying the interactions of Ru(II)/Ru(III) complexes with biological receptors, which can facilitate the rational design of ruthenium-based drugs.


Assuntos
Antineoplásicos , Complexos de Coordenação , Diabetes Mellitus Tipo 2 , Farmácia , Rutênio , Humanos , Complexos de Coordenação/farmacologia , Rutênio/farmacologia , Preparações Farmacêuticas , Antineoplásicos/farmacologia
2.
Eur J Clin Microbiol Infect Dis ; 41(6): 961-969, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35585442

RESUMO

Haemophilus influenzae is a human-specific pathogen responsible for respiratory tract infections, meningitis, and sepsis. The study aimed to characterize antibiotic resistance in H. influenzae strains isolated from patients with lower respiratory tract infections over 15 years in Poland. The minimum inhibitory concentrations (MICs) of clinically relevant antibiotics were determined by broth microdilution method. Screening for beta-lactam resistance was performed in all isolates following EUCAST recommendation. Finally, relevant changes in penicillin-binding protein 3 (PBP3) were detected by PCR screening. Of the 1481 isolates collected between 2005 and 2019, 12.6%, 0.2%, 17.1%, and 0.2% were resistant to ampicillin, amoxicillin/clavulanate, cefuroxime, and ceftriaxone, respectively. Among them, 74.4% (1102/1481) of isolates were categorized as BLNAS (ß-lactamase negative, ampicillin-susceptible), 13.0% (192/1481) as BLNAS with modified PBP3 (mutations in ftsI gene), 2.6% (39/1481) as BLNAR (ß-lactamase negative, ampicillin-resistant), and 0.2% had PBP3 modifications typical for high-BLNAR. Production of ß-lactamase characterized 9.7% of isolates (8.6% BLPAR-ß-lactamase-positive, ampicillin-resistant, and 1.1% BLPACR-ß-lactamase-positive, amoxicillin-clavulanate resistant). Three isolates with PBP3 modifications typical for high-BLNAR proved resistant to ceftriaxone (MIC > 0.125 mg/L). Resistance to ciprofloxacin, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole was observed in 0.1%, 0.5%, 1.6%, and 24.7% of isolates, respectively. This is the first report of Polish H. influenzae isolates resistant to third-generation cephalosporins. Polish H. influenzae isolates demonstrate similar susceptibility trends as in many other countries. The substantial proportion of ß-lactam-resistant isolates and the emergence of those resistant to third-generation cephalosporins are of great concern and should be under surveillance.


Assuntos
Infecções por Haemophilus , Infecções Respiratórias , Combinação Amoxicilina e Clavulanato de Potássio , Ampicilina/farmacologia , Antibacterianos/farmacologia , Ceftriaxona , Farmacorresistência Bacteriana , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/genética , Humanos , Testes de Sensibilidade Microbiana , Polônia/epidemiologia , Infecções Respiratórias/epidemiologia , beta-Lactamases/genética
3.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443474

RESUMO

Numerous plant compounds and their metal-ion complexes exert antioxidative, anti-inflammatory, anticancer, and other beneficial effects. This review highlights the different bioactivities of flavonoids, chromones, and coumarins and their metal-ions complexes due to different structural characteristics. In addition to insight into the most studied antioxidative properties of these compounds, the first part of the review provides a comprehensive overview of exogenous and endogenous sources of reactive oxygen and nitrogen species, oxidative stress-mediated damages of lipids and proteins, and on protective roles of antioxidant defense systems, including plant-derived antioxidants. Additionally, the review covers the anti-inflammatory and antimicrobial activities of flavonoids, chromones, coumarins and their metal-ion complexes which support its application in medicine, pharmacy, and cosmetology.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Complexos de Coordenação/química , Íons/química , Metais/química , Compostos Fitoquímicos/farmacologia , Anti-Inflamatórios/química , Antioxidantes/química , Radicais Livres/metabolismo , Humanos , Compostos Fitoquímicos/química , Plantas/química
4.
J Antimicrob Chemother ; 75(3): 512-520, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789384

RESUMO

OBJECTIVES: We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions. METHODS: We whole-genome sequenced 12 254 pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes. An SNP tree was built using Gubbins. Temporal spread was reconstructed using a birth-death model. RESULTS: We identified tet(S/M) in 131 pneumococcal isolates and none carried other known tet genes. Tetracycline susceptibility testing results were available for 121 tet(S/M)-positive isolates and all were resistant. A majority (74%) of tet(S/M)-positive isolates were from South Africa and caused invasive diseases among young children (59% HIV positive, where HIV status was available). All but two tet(S/M)-positive isolates belonged to clonal complex (CC) 230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sublineage predicted to exhibit resistance to penicillin, co-trimoxazole, erythromycin and tetracycline. The birth-death model detected an unrecognized outbreak of this sublineage in South Africa between 2000 and 2004 with expected secondary infections (effective reproductive number, R) of ∼2.5. R declined to ∼1.0 in 2005 and <1.0 in 2012. The declining epidemic could be related to improved access to ART in 2004 and introduction of pneumococcal conjugate vaccine (PCV) in 2009. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sublineage. CONCLUSIONS: The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognized outbreak of CC230 in South Africa. Capsular switching in this MDR sublineage highlighted its potential to continue to cause disease in the post-PCV13 era.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Antibacterianos/farmacologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Humanos , Tipagem de Sequências Multilocus , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas , Sorogrupo , África do Sul/epidemiologia , Resistência a Tetraciclina/genética
5.
PLoS Pathog ; 14(11): e1007438, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30475919

RESUMO

Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939-1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.


Assuntos
Infecções Pneumocócicas/imunologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Teorema de Bayes , Portador Sadio/epidemiologia , Evolução Molecular , Genética Populacional/métodos , Humanos , Filogenia , Infecções Pneumocócicas/transmissão , Vacinas Pneumocócicas/imunologia , Dinâmica Populacional , Prevalência , Sorogrupo , Sorotipagem/métodos , Streptococcus pneumoniae/patogenicidade , Vacinas Conjugadas , Sequenciamento Completo do Genoma/métodos
6.
Eur J Clin Microbiol Infect Dis ; 39(6): 1185-1191, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32096107

RESUMO

We evaluated the in vitro effectiveness of temocillin and several commonly used antimicrobials against Enterobacterales bacteria in isolates from Polish patients. We tested 400 isolates: 260 extended-spectrum ß-lactamase (ESBL)- and/or ampC ß-lactamase (AmpC)-producing isolates; 40 Klebsiella pneumoniae carbapenemase (KPC)-producing isolates; and 100 ESBL-, AmpC-, and KPC-negative isolates. The minimal inhibitory concentrations (MICs) of temocillin and 16 other antimicrobials were determined by reference microdilution. We also determined the activities of fosfomycin and ceftazidime/avibactam in KPC-producing isolates. The antibiotic sensitivities were interpreted according to EUCAST, BSAC, and CLSI criteria. Overall, 91% of the isolates were susceptible to temocillin using the urinary tract infection breakpoint (≤ 32 mg/L), and 61.8% were susceptible using the systemic infection breakpoint (≤ 8 mg/L). Meropenem and imipenem were the most active drugs (MIC50 values of 0.06 and 0.5 mg/L, respectively). Colistin and ertapenem (both MIC50 = 0.12 mg/L) were less active than meropenem or imipenem, but some strains were 77% susceptible to each of them. Among the KPC-producing isolates, 42.5% had MIC values of ≤ 32 mg/L (urinary tract infection breakpoint), but 100% were resistant to temocillin (systemic infection breakpoint). Ceftazidime/avibactam was active against 100% of the KPC-producing isolates, and fosfomycin was active against 40%. The empirical susceptibility rate observed among the urinary isolates suggests that temocillin may be considered as an alternative to carbapenems in the absence of KPC-producing bacteria. With regard to isolates from other sources, temocillin might be useful as a documented therapy agent or an empirical treatment in hospitals with a low prevalence of ESBL/AmpC-producing strains.


Assuntos
Antibacterianos/farmacologia , Gammaproteobacteria/efeitos dos fármacos , Gammaproteobacteria/enzimologia , Penicilinas/farmacologia , beta-Lactamases/metabolismo , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana , Gammaproteobacteria/classificação , Gammaproteobacteria/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Klebsiella/classificação , Klebsiella/efeitos dos fármacos , Klebsiella/enzimologia , Klebsiella/isolamento & purificação , Testes de Sensibilidade Microbiana , Polônia
7.
Eur J Clin Microbiol Infect Dis ; 39(10): 1865-1878, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32409955

RESUMO

The aim of our study was to investigate phenotypic and genotypic features of streptococci misidentified (misID) as Streptococcus pneumoniae, obtained over 20 years from hospital patients in Poland. Sixty-three isolates demonstrating microbiological features typical for pneumococci (optochin susceptibility and/or bile solubility) were investigated by phenotypic tests, lytA and 16S rRNA gene polymorphism and whole-genome sequencing (WGS). All isolates had a 6-bp deletion in the lytA 3' terminus, characteristic for Mitis streptococc and all but two isolates lacked the pneumococcal signature cytosine at nucleotide position 203 in the 16S rRNA genes. The counterparts of psaA and ply were present in 100% and 81.0% of isolates, respectively; the spn9802 and spn9828 loci were characteristic for 49.2% and 38.1% of isolates, respectively. Phylogenetic trees and networks, based on the multilocus sequence analysis (MLSA) scheme, ribosomal multilocus sequence typing (rMLST) scheme and core-genome analysis, clearly separated investigated isolates from S. pneumoniae and demonstrated the polyclonal character of misID streptococci, associated with the Streptococcus pseudopneumoniae and Streptococcus mitis groups. While the S. pseudopneumoniae clade was relatively well defined in all three analyses, only the core-genome analysis revealed the presence of another cluster comprising a fraction of misID streptococci and a strain proposed elsewhere as a representative of a novel species in the Mitis group. Our findings point to complex phylogenetic and taxonomic relationships among S. mitis-like bacteria and support the notion that this group may in fact consist of several distinct species.


Assuntos
Infecções Estreptocócicas/epidemiologia , Streptococcus mitis/isolamento & purificação , Streptococcus/isolamento & purificação , Técnicas de Tipagem Bacteriana , Erros de Diagnóstico , Feminino , Humanos , Masculino , Filogenia , Polônia/epidemiologia , RNA Ribossômico 16S , Infecções Estreptocócicas/microbiologia , Streptococcus/genética , Streptococcus mitis/genética , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação
8.
Euro Surveill ; 24(14)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30968827

RESUMO

BackgroundThe total incidence of invasive meningococcal disease (IMD) in Europe has been declining in recent years; however, a rising incidence due to serogroup W (MenW), predominantly sequence type 11 (ST-11), clonal complex 11 (cc11), was reported in some European countries.AimThe aim of this study was to compile the most recent laboratory surveillance data on MenW IMD from several European countries to assess recent trends in Europe.MethodsIn this observational, retrospective study, IMD surveillance data collected from 2013-17 by national reference laboratories and surveillance units from 13 European countries were analysed using descriptive statistics.ResultsThe overall incidence of IMD has been stable during the study period. Incidence of MenW IMD per 100,000 population (2013: 0.03; 2014: 0.05; 2015: 0.08; 2016: 0.11; 2017: 0.11) and the proportion of this serogroup among all invasive cases (2013: 5% (116/2,216); 2014: 9% (161/1,761); 2015: 13% (271/2,074); 2016: 17% (388/2,222); 2017: 19% (393/2,112)) continuously increased. The most affected countries were England, the Netherlands, Switzerland and Sweden. MenW was more frequent in older age groups (≥ 45 years), while the proportion in children (< 15 years) was lower than in other age groups. Of the culture-confirmed MenW IMD cases, 80% (615/767) were caused by hypervirulent cc11.ConclusionDuring the years 2013-17, an increase in MenW IMD, mainly caused by MenW cc11, was observed in the majority of European countries. Given the unpredictable nature of meningococcal spread and the epidemiological potential of cc11, European countries may consider preventive strategies adapted to their contexts.


Assuntos
Infecções Meningocócicas/epidemiologia , Neisseria meningitidis/classificação , Neisseria meningitidis/genética , Vigilância da População/métodos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Infecções Meningocócicas/diagnóstico , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Neisseria meningitidis/isolamento & purificação , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Sorogrupo , Adulto Jovem
9.
Euro Surveill ; 23(20)2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29790460

RESUMO

Invasive meningococcal disease surveillance in Europe combines isolate characterisation and epidemiological data to support public health intervention. A representative European Meningococcal Strain Collection (EMSC) of IMD isolates was obtained, and whole genome sequenced to characterise 799 EMSC isolates from the epidemiological year July 2011-June 2012. To establish a genome library (GL), the isolate information was deposited in the pubMLST.org/neisseria database. Genomes were curated and annotated at 2,429 meningococcal loci, including those defining clonal complex, capsule, antigens, and antimicrobial resistance. Most genomes contained genes encoding B (n = 525; 65.7%) or C (n = 163; 20.4%) capsules; isolates were genetically highly diverse, with >20 genomic lineages, five of which comprising 60.7% (n = 485) of isolates. There were >350 antigenic fine-types: 307 were present once, the most frequent (P1.7-2,4:F5-1) comprised 8% (n = 64) of isolates. Each genome was characterised for Bexsero Antigen Sequence Typing (BAST): 25.5% (n = 204) of isolates contained alleles encoding the fHbp and/or the PorA VR1 vaccine component, but most genomes (n = 513; 64.2%) did not contain the NadA component. EMSC-GL will support an integrated surveillance of disease-associated genotypes in Europe, enabling the monitoring of hyperinvasive lineages, outbreak identification, and supporting vaccine programme implementation.


Assuntos
Genes Bacterianos/genética , Biblioteca Genômica , Meningite Meningocócica/microbiologia , Infecções Meningocócicas/microbiologia , Neisseria meningitidis Sorogrupo B/genética , Neisseria meningitidis/classificação , Neisseria meningitidis/genética , Sequenciamento Completo do Genoma , Europa (Continente) , Loci Gênicos , Variação Genética , Genoma Bacteriano , Genômica , Genótipo , Humanos , Meningite Meningocócica/genética , Infecções Meningocócicas/genética , Epidemiologia Molecular , Neisseria meningitidis/isolamento & purificação , Vigilância da População , Sorogrupo
10.
Postepy Dermatol Alergol ; 34(2): 97-103, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28507486

RESUMO

Discoloration are symptoms of skin aging. They are connected with presence of melanin and lipofuscin, whose excess and abnormal distribution in the skin cause dark spots to appear. Melanin is formed under the influence of tyrosinase during melanogenesis. Its content changes with age, which may be a result of menopause. Lipofuscin is another example of the age pigment. It is composed of proteins, lipids and carbohydrates. It is described as an age pigment because its content increases with age. The formation and accumulation of lipofuscin is inevitable and leads to cell and homeostasis dysfunction because it reduces the proteasome activity.

11.
Anal Bioanal Chem ; 408(16): 4319-27, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27086021

RESUMO

A highly efficient recognition unit based on surface-enhanced Raman spectroscopy (SERS) was developed as a promising, fast, and sensitive tool for detection of meningococcal meningitis, which is an extremely serious and often fatal disease of the nervous system (an inflammation of the lining around the brain and spinal cord). The results of this study confirmed that there were specific differences in SERS spectra between cerebrospinal fluid (CSF) samples infected by Neisseria meningitidis and the normal CSF, suggesting a potential role for neopterin in meningococcal meningitis detection and screening applications. To estimate the best performance of neopterin as a marker of bacterial infection, principal component analysis (PCA) was performed in a selected region (640-720 cm(-1)) where the most prominent SERS peak at 695 cm(-1) arising from neopterin was observed. The calculated specificity of 95 % and sensitivity of 98 % clearly indicate the effective diagnostic efficiency for differentiation between infected and control samples. Additionally, the limit of detection (LOD) of neopterin in CSF clinical samples was estimated. The level of neopterin was significantly higher in CSF samples infected by N. meningitidis (48 nmol/L), compared to the normal (control) group (4.3 nmol/L). Additionally, this work presents a new type of SERS-active nanostructure, based on polymer mats, that allows simultaneous filtration, immobilization, and enhancement of the Raman signal, enabling detection of spectra from single bacterial cells of N. meningitidis present in CSF samples. This provides a new possibility for fast and easy detection of bacteria in CSF and other clinical body fluids on a time scale of seconds. This method of detection produces consistent results faster and cheaper than traditional laboratory techniques, demonstrates the powerful potential of SERS for detection of disease, and shows the viability of future development in healthcare applications.


Assuntos
Líquido Cefalorraquidiano/química , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/diagnóstico , Neopterina/líquido cefalorraquidiano , Análise Espectral Raman/métodos , Humanos , Limite de Detecção , Meningite Meningocócica/microbiologia , Neisseria meningitidis/genética , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis/fisiologia
12.
Med Sci Monit ; 22: 4661-4669, 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-27899788

RESUMO

BACKGROUND Plasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism. MATERIAL AND METHODS The selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates. RESULTS Serum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=-0.21; p<0.01) and between TSH and PLTP (r=-0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=-0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=-0.24; p<0.001) has been demonstrated as well. CONCLUSIONS The decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol/sangue , Hipotireoidismo/sangue , Proteínas de Transferência de Fosfolipídeos/sangue , Tireotropina/sangue , Alcoolismo/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/sangue
13.
Postepy Hig Med Dosw (Online) ; 70(0): 1087-1094, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27708212

RESUMO

Morphology of senescent cells is constantly changing at the molecular level, which in turn leads to disruption of their function. It is connected with reduced ability to synthesize extracellular matrix (ECM) and leads to the dysfunction of integrin adhesion molecules and adhesion clusters. In skin, these factors cause a loss of communication between the extracellular matrix and fibroblasts. This contributes to the appearance of signs of aging. The aim of this study is to draw attention to the very important molecule such as paxillin, which is an adaptor protein with mass of 68 kDa. This family of proteins includes Hic-5, PaxB and leupaxin. Paxillin binds to actin-binding proteins such as vinculin, actopaxin, and kinases (e.g. Integrin-linked kinase (ILK)). Moreover, it plays an important role in the integrity of the matrix, because it transduces transmembrane signaling between integrins and growth factors. Paxillin is a scaffold protein, activating the arrangement and organization of the cytoskeleton. Signaling through paxillin affects the long-term changes in gene expression, cell proliferation, and organization of the ECM. Correct functioning of the ECM is important for the wound healing processes and regeneration of tissues or tissue repair. Decrease or lack of paxillin expression results in changes in the structure and integrity of the ECM, which are manifested by aging of cells and organs. Restoration of the cellular matrix connections would be a significant element in the processes related to the anti-aging activities.


Assuntos
Envelhecimento , Paxilina/metabolismo , Transdução de Sinais , Pele/metabolismo , Animais , Proteínas do Citoesqueleto/metabolismo , Matriz Extracelular/metabolismo , Humanos , Integrinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Paxilina/fisiologia , Ligação Proteica , Fenômenos Fisiológicos da Pele
14.
Pol J Microbiol ; 64(4): 313-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26999951

RESUMO

Neisseria meningitidis is a commensal of human nasopharynx and humans are the only known reservoir and host of this bacterium. It is also known as a dangerous and devastating pathogen, and infection with N. meningitidis may lead to rapidly progressing septicemia or meningitis. These severe infections, called invasive meningococcal disease (IMD), are one of the major public health threats worldwide. IMD may occur sporadically, but also in outbreaks, epidemics, and pandemics. Most of the IMD cases in the world are caused by isolates of genetically related groups, clonal complexes (CC), including those with special epidemiological significance called hyperinvasive clonal complexes. It is still unknown why some of them may persist for decades, whereas other are quickly replaced and disappear. As a consequence, the epidemiological situation of IMD is variable worldwide and greatly depends on the emergence and widespread of clones belonging to hyperinvasive clonal complexes. Their occurrence has serious implications for health policy, requiring often mass immunization campaigns. Paradoxically, alarming situations caused by hyperinvasive CCs stimulated the development and introduction of new vaccines against meningococci. Despite the unquestionable success of these vaccines, isolates of hyperinvasive clones constitute a permanent public health threat, because they are constantly circulating and able to modify their antigenic profiles to escape the host immune response. Therefore, continuous monitoring of meningococcal isolates including thorough molecular typing is indispensable and fundamental for taking appropriate preventive measures.


Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/genética , Neisseria meningitidis/imunologia , Surtos de Doenças , Humanos
15.
Med Pr ; 66(4): 539-48, 2015.
Artigo em Polonês | MEDLINE | ID: mdl-26536970

RESUMO

BACKGROUND: The aim of the study was to evaluate serum levels of the target enzyme for H2S toxicity--cytochrome c oxidase (COX) and enzymes involved in the synthesis of H2S--cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) in copper mine miners. MATERIAL AND METHODS: The initial and basic study was conducted respectively in 237 and 88 miners, working in 2 mining shafts: I--no H2S emissions recorded in the last 10 years (study group A) and II--H2S emissions occurred (study group B). A medical examination was performed and 10 ml of blood was collected from miners immediately after exiting the mine. RESULTS: There were no clinical or biochemical changes typical for H2S toxicity. Sulfhemoglobine was undetectable and there were no changes in the red-ox system. However, in group B, regulatory changes were found; a tendency to higher concentration of CBS and CSE, a higher activity of angiotensin converting enzyme (ACE) compared to group A (p<0.05) and a linear relationship between ACE and CSE (r=0.6927; p<0.001). It has been shown that cigarette smoking decreases COX (p<0.05), however, in miners working in shaft II, the decreased level of COX may result also from the presence of H2S in the gaseous emissions. CONCLUSIONS: COX concentration can be a sensitive indicator of exposure to H2S. The measurements of blood H2S concentrations carried out in workplaces should explain the cause of the changes observed in the COX, CBS and CSE activity.


Assuntos
Cobre/efeitos adversos , Cistationina beta-Sintase/sangue , Cistationina gama-Liase/sangue , Complexo IV da Cadeia de Transporte de Elétrons/sangue , Sulfeto de Hidrogênio/metabolismo , Mineração , Doenças Profissionais/metabolismo , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Mineradores , Doenças Profissionais/diagnóstico , Exposição Ocupacional/efeitos adversos , Polônia , Estudos Retrospectivos
16.
Prz Menopauzalny ; 14(1): 53-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26327889

RESUMO

Current literature data indicate that progerin, which is a mutant of lamin A, may be one of several previously known physiological biomarkers of the aging process which begins at the age of 30. Lamins belong to the family of intermediate filaments type V and are an important component of the nuclear envelope (NE). The physiological processes of an alternative splicing of LMNA (lamin A/C) gene and posttranslational processing result in the formation of different variants of this gene. Prelamin A is generated in cytosol and modified by respective enzymes. In the final step, 15-aa peptide is released at the C-terminus, resulting in mature lamin A. Point mutation of cytosine to thymine at position 1824 in exon 11 of LMNA gene causes a truncated form of lamin A, which is defined as progerin. In the course of time, progerin is mainly found in skin fibroblasts and reticular layers of terminally differentiated keratinocytes. Changes take place in the nucleus and they are similar to those observed in patients with Hutchinson-Gilford progeria syndrome and refer mainly to an increase in the amount of reactive oxygen species which reduce the level of antioxidant enzymes, DNA damage and histone modification. There are still pending studies on working out new anti-aging strategies and the skin is the main area of research. Biomimetic peptides (analogues of elafin) are used in cosmetics to reduce the formation of progerin.

17.
J Clin Microbiol ; 52(7): 2647-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24759721

RESUMO

This study evaluated the usefulness of the Pneumotest-Latex assay for serotyping Streptococcus pneumoniae isolates directly in clinical samples. With an agreement of 88.1% with a PCR-based reference method, this test can be a useful tool for this study purpose, especially in clinical laboratories that do not have access to nucleic acid amplification technologies.


Assuntos
Técnicas de Tipagem Bacteriana/métodos , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Humanos , Testes de Fixação do Látex/métodos , Sorotipagem/métodos
18.
Pol Merkur Lekarski ; 36(212): 79-87, 2014 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-24720101

RESUMO

Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD risk groups in the age > 19 years. At these work research findings were described above PPV23 and PCV13 at adults and world recommendations of applying both vaccines in risk groups from 19 years up to the advanced years. Also Polish recommendations of optimum applying of these vaccines were presented. They are recommending applying PCV13 at first in them, while PPV23, if to her readings exist should be given to > or = 8 of weeks from PCV13. In persons > or = 19 years which earlier received 1 or should receive more PPV23 doses first PCV13 dose should be given after the year or later than the last PPV23 dose, and then again PPV23 > or = 8 of weeks from PCV13 and the second PPV23 dose not earlier than 5 years from last PPV23. If the PPV23 application seems to be justified, it is irrespective of the more previous state vaccination against pneumococci, PCV13 should be given to as first.


Assuntos
Bacteriemia/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/uso terapêutico , Pneumonia/prevenção & controle , Adulto , Envelhecimento/imunologia , Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Feminino , Humanos , Memória Imunológica , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Pneumonia/epidemiologia , Polônia/epidemiologia , Guias de Prática Clínica como Assunto , Fatores de Risco , Adulto Jovem
19.
Hum Vaccin Immunother ; 20(1): 2301186, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38173392

RESUMO

Invasive meningococcal disease (IMD) is an acute life-threatening infection caused by the gram-negative bacterium, Neisseria meningitidis. Globally, there are approximately half a million cases of IMD each year, with incidence varying across geographical regions. Vaccination has proven to be successful against IMD, as part of controlling outbreaks, and when incorporated into national immunization programs. The South-Eastern Europe Meningococcal Advocacy Group (including representatives from Croatia, the Czech Republic, Greece, Hungary, Poland, Romania, Serbia, Slovenia and Ukraine) was formed in order to discuss the potential challenges of IMD faced in the region. The incidence of IMD across Europe has been relatively low over the past decade; of the countries that came together for the South-Eastern Meningococcal Advocacy Group, the notification rates were lower than the European average for some country. The age distribution of IMD cases was highest in infants and children, and most countries also had a further peak in adolescents and young adults. Across the nine included countries between 2010 and 2020, the largest contributors to IMD were serogroups B and C; however, each individual country had distinct patterns for serogroup distribution. Along with the variations in epidemiology of IMD between the included countries, vaccination policies also differ.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Criança , Lactente , Adolescente , Adulto Jovem , Humanos , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/microbiologia , Europa (Continente)/epidemiologia , República Tcheca , Vacinação , Sorogrupo
20.
Cent Eur J Public Health ; 21(4): 233-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24592732

RESUMO

BACKGROUND: An important development in the field of adult pneumococcal vaccination since the last Consensus Statement, published by the Expert Panel of Central and Eastern Europe and Israel (the Region) in September 2012, was the licensure of the 13-valent pneumococcal conjugate vaccine (PCV13) for adults aged 50 years and older. DISCUSSION: The Expert Panel has developed this Position Statement as an update to its previous Consensus to address the following topics which are likely to be on the agenda of national scientific societies during the ongoing updates of vaccination recommendations in the Region: the availability of a pneumococcal conjugate vaccine for adults over 50 years of age, the available clinical evidence on its use in adults, and the future place of conjugate vaccines in adult pneumococcal vaccination. The Expert Panel concluded that there is sufficient epidemiologic immunogenicity and safety evidence to use PCV 13 in adults over 50 years of age. RESULTS: The use of conjugate vaccine induces immunological memory and can overcome some limitations associated with the plain polysaccharide vaccine (PPV). It was also agreed that, if the use of PPV is considered appropriate, PCV13 should be administered first, regardless of prior pneumococcal vaccination status.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Europa (Continente) , Humanos , Israel , Pessoa de Meia-Idade , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Guias de Prática Clínica como Assunto
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