phosphonates
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Praktičtí lékaři a gynekologové zajišťují léčbu perorálními aminobisfosfonáty u lidí, kteří podle anamnézy, klinického a laboratorního vyšetření a výsledku osteodenzitometrie (BMD v některém ze standardních míst skeletu ≤ 2,5 T skóre) trpí primární (involuční nebo postmenopauzální) osteoporózou nebo utrpěli nízkotraumatickou zlomeninu, ale nemají velmi vysoké riziko zlomenin. Pacienty, u kterých je zjištěna suspektní sekundární osteoporóza, a pacienty s velmi vysokým rizikem zlomenin při primární osteoporóze předávají do péče ambulantních specialistů. Zejména však mají praktičtí lékaři a gynekologové nezaměnitelné postavení při včasné prevenci primární a sekundární osteoporózy, která zůstává vzhledem k nákladnosti screeningu, diagnostiky a léčby onemocnění v rozsáhlé populaci osob starších 50 let rozhodujícím opatřením pro snížení incidence nízkotraumatických zlomenin. Článek zmiňuje populační program časného záchytu osteoporózy, doporučené postupy a praktické aspekty léčby primární osteoporózy perorálními aminobisfosfonáty.
General practitioners and gynecologists provide treatment with oral aminobisphosphonates in people who, according to their medical history and results of clinical, laboratory, and bone densitometry examinations have primary (involutionary or postmenopausal) osteoporosis, or have suffered a low-traumatic fracture but do not have a very high risk of fractures. Patients who are diagnosed or suspected of secondary osteoporosis and patients with a very high risk of fractures in primary osteoporosis are referred to outpatient specialists. In particular, however, general practitioners and gynecologists have an unmistakable position in the early prevention of primary and secondary osteoporosis, which remains a decisive measure for reducing the incidence of low-traumatic fractures due to the cost of screening, diagnosis, and treatment of the disease in a large population of people over 50 years of age. The article mentions the population-based program for early detection of osteoporosis, recommended procedures, and practical aspects of the treatment of primary osteoporosis using oral aminobisphosphonates.
- MeSH
- adherence k farmakoterapii MeSH
- bisfosfonátová osteonekróza čelistí etiologie prevence a kontrola terapie MeSH
- denzitometrie MeSH
- fraktury kostí etiologie prevence a kontrola MeSH
- inhibitory kostní resorpce farmakologie škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- organofosfonáty farmakologie škodlivé účinky terapeutické užití MeSH
- osteoporóza * epidemiologie etiologie farmakoterapie prevence a kontrola MeSH
- riziko MeSH
- služby preventivní péče metody MeSH
- statistika jako téma MeSH
- vápník aplikace a dávkování MeSH
- vitamin D aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Copper radioisotopes can be used for imaging as well as for therapy and, thus, can form ideal theranostic pairs. The Cu(II) complexes of cross-bridged cyclam (cb-cyclam) derivatives are considered to be highly stable in vivo. However, the complexes are mostly formed under harsh conditions not compatible with sensitive biomolecules. Here, a new class of cb-cyclam derivatives, cross-bridged bis(phosphinate)cyclams ("cb-BPC"), were investigated. Ligands with one or two methylene-bis(phosphinate) -CH2-PO2H-CH2-PO2H(R) (R = H, OH, substituted alkyl) pendant arms were synthesized. Bifunctionalization on the distant phosphorus atom was carried out by employing P-nitrobenzyl (R = CH2-Ph-4-NO2) precursors and/or, for cb-BPC with two bis(phosphinate) pendant arms, by reactions of silyl-phosphites obtained by silylation of their P(O)-H fragments. The reactive bifunctional groups include amine, carboxylate, azide, isothiocyanate, maleimide and/or tetrazine, and also their orthogonally reactive combination in a single molecule of chelator. The cb-BPCs with one bis(phosphinate) arm were not efficiently radiolabelled with 64Cu. The cb-BPCs with two pendant arms were radiolabelled even at room temperature and with only a small excess of chelator, leading to a high specific activity. Radiolabelling was fully comparable with that of analogous bis(phosphinate) derivatives of cyclam and identical radiolabelling of cyclam and cb-cyclam derivatives was observed for the first time. The cb-BPCs with two bis(phosphinate) pendant arms represent a new class of rigid chelators for copper radioisotopes that are easily synthetically modifiable, highly hydrophilic and radiolabelled under mild conditions.
- Publikační typ
- časopisecké články MeSH
Fosfomycin (FOS) is an effective antibiotic against multidrug-resistant Enterobacterales, but its effectiveness is reducing. Little is known on the current prevalence of FosA enzymes in low-risk pathogens, such as Citrobacter freundii. The aim of the study was the molecular characterization of a carbapenemase- and FosA-producing C. freundii collected in Italy. AK867, collected in 2023, showed an XDR profile, retaining susceptibility only to colistin. AK867 showed a FOS MIC >128 mg/L by ADM. Based on WGS, AK867 belonged to ST116 and owned a wide resistome, including fosA3, blaKPC-2, and blaVIM-1. fosA3 was carried by a conjugative pKPC-CAV1312 plasmid of 320,480 bp, on a novel composite transposon (12,907 bp). FosA3 transposon shared similarities with other fosA3-harboring pKPC-CAV1312 plasmids among Citrobacter spp. We report the first case of FosA3 production in clinical carbapenemase-producing C. freundii ST116. The incidence of FosA3 enzymes is increasing among Enterobacterales, affecting even low-virulence pathogens, as C. freundii.
- MeSH
- antibakteriální látky * farmakologie MeSH
- bakteriální proteiny * genetika metabolismus MeSH
- beta-laktamasy * genetika metabolismus MeSH
- Citrobacter freundii * genetika enzymologie účinky léků MeSH
- enterobakteriální infekce * mikrobiologie MeSH
- fosfomycin * farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence genetika MeSH
- plazmidy genetika MeSH
- sekvenování celého genomu MeSH
- transpozibilní elementy DNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Itálie MeSH
Fosfomycin-resistant FosA8-producing Enterobacterales are uncommon strains with extremely low incidence in Europe, based on only three reports in the literature. We detected FosA8-producing Escherichia coli ST131 in clinical isolates from two patients admitted in February 2023 to a rehabilitation unit in Italy. The occurrence of rare fosA-like genes in the high-risk clone ST131 is of clinical relevance. The dissemination of FosA-producing E. coli, although still at low levels, should be continuously monitored.
- MeSH
- antibakteriální látky * farmakologie terapeutické užití MeSH
- bakteriální léková rezistence MeSH
- beta-laktamasy genetika metabolismus MeSH
- Escherichia coli * izolace a purifikace genetika účinky léků MeSH
- fosfomycin farmakologie terapeutické užití MeSH
- infekce vyvolané Escherichia coli * mikrobiologie epidemiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Itálie MeSH
Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA and RNA synthesis, resulting in a reduction in cell growth. Therefore, inhibitors of this enzyme have potential to control infections, caused by Plasmodium falciparum and Plasmodium vivax, Trypanosoma brucei, Mycobacterium tuberculosis, and Helicobacter pylori. Five compounds synthesized here that contain a purine base covalently linked by a prolinol group to one or two phosphonate groups have Ki values ranging from 3 nM to >10 μM, depending on the structure of the inhibitor and the biological origin of the enzyme. X-ray crystal structures show that, on binding, these prolinol-containing inhibitors stimulated the movement of active site loops in the enzyme. Against TBr in cell culture, a prodrug exhibited an EC50 of 10 μM. Thus, these compounds are excellent candidates for further development as drug leads against infectious diseases as well as being potential anticancer agents.
- MeSH
- inhibitory enzymů * farmakologie chemie chemická syntéza MeSH
- katalytická doména MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- pentosyltransferasy * antagonisté a inhibitory metabolismus MeSH
- racionální návrh léčiv * MeSH
- Trypanosoma brucei brucei účinky léků enzymologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Fosfomycin, antibiotikum objevené v roce 1969, zažívá svou renesanci především v léčbě infekcí způsobených multirezistentními gram-negativními patogeny. Díky kombinaci svého jedinečného mechanismu účinku, širokého spektra účinnosti, příznivé úrovně rezistence, dobrého tkáňového průniku a nízké incidence nežádoucích účinků představuje unikátní terapeutickou alternativu. Cílem tohoto článku je shrnout základní farmakologické charakteristiky fosfomycinu s důrazem na jeho intravenózní formu.
Fosfomycin, an antibiotic discovered in 1969, is experiencing a renaissance, particularly in the treatment of infections caused by multidrug-resistant Gram-negative pathogens. The combination of its unique mechanism of action, broad spectrum of activity, favourable level of resistance, good tissue penetration and low incidence of adverse events makes it a valuable therapeutic alternative. The aim of this article is to summarize the main pharmacological characteristics of fosfomycin with emphasis on its intravenous form.
- MeSH
- chirurgická náhrada chlopně MeSH
- dospělí MeSH
- endokarditida * farmakoterapie MeSH
- fosfomycin * farmakologie terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetná bakteriální léková rezistence účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Prostate cancer is the most common malignant solid tumour in men aged >70 years and is the second most common cause of death from oncological circumstances. AIM: To evaluate the effect of different short-term prophylactic antibiotic regimens in transrectal prostate biopsy (PB) on the incidence of infectious complications. METHODS: Patients who underwent transrectal ultrasound-guided PB between January 2021 and December 2022 were included in the prospective randomized study. According to the regimen of prophylaxis, patients were randomized into three groups: (1) fosfomycin trometamol 3 g, 3 h before the procedure + ciprofloxacin 500 mg, 2 h before the procedure; (2) fosfomycin trometamol 3 g, 3 h before and 24 h after the procedure; (3) ciprofloxacin 500 mg 12, 2 h before the procedure, and 12 h after the procedure. A rectal swab was performed 1-2 weeks before PB to evaluate the culture findings. Complications were evaluated during follow-up visits within one month after PB. FINDINGS: In the monitored period, 605 PBs were performed, and 544 patients met the inclusion criteria (184, 161, and 199 in groups 1, 2, and 3). Infectious complications occurred in 10 cases (1.83%), namely 3, 4, and 3 according to patient groups. There was no statistically significant difference between the individual groups. None of the patients required hospitalization and all were free of symptoms of sepsis. CONCLUSION: Short-term antibiotic prophylaxis in PB using fosfomycin trometamol, ciprofloxacin, or their combination appears to be effective. Fosfomycin trometamol is a suitable alternative to fluoroquinolone antibiotics.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- antibiotická profylaxe metody MeSH
- biopsie škodlivé účinky metody MeSH
- ciprofloxacin terapeutické užití MeSH
- fosfomycin * terapeutické užití MeSH
- lidé MeSH
- prospektivní studie MeSH
- prostata * diagnostické zobrazování patologie MeSH
- rektum MeSH
- tromethamin MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
The development of new antiviral agents such as nucleoside analogues or acyclic nucleotide analogues (ANPs) and prodrugs thereof is an ongoing task. We report on the synthesis of three types of lipophilic triphosphate analogues of (R)-PMPA and dialkylated diphosphate analogues of (R)-PMPA. A highly selective release of the different nucleotide analogues ((R)-PMPA-DP, (R)-PMPA-MP, and (R)-PMPA) from these compounds was achieved. All dialkylated (R)-PMPA-prodrugs proved to be very stable in PBS as well as in CEM/0 cell extracts and human plasma. In primer extension assays, both the monoalkylated and the dialkylated (R)-PMPA-DP derivatives acted as (R)-PMPA-DP as a substrate for HIV-RT. In contrast, no incorporation events were observed using human polymerase γ. The dialkylated (R)-PMPA-compounds exhibited significant anti-HIV efficacy in HIV-1/2 infected cells (CEM/0 and CEM/TK-). Remarkably, the dialkylated (R)-PMPA-MP derivative 9a showed a 326-fold improved activity as compared to (R)-PMPA in HIV-2 infected CEM/TK- cells as well as a very high SI of 14,000. We are convinced that this study may significantly contribute to advancing antiviral agents developed based on nucleotide analogues in the future.
- MeSH
- adenin MeSH
- HIV-2 MeSH
- látky proti HIV * chemie MeSH
- lidé MeSH
- nukleotidy MeSH
- organofosfonáty * chemie MeSH
- prekurzory léčiv * chemie MeSH
- tenofovir farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A miniature probe for electromembrane extraction is developed and constructed. The tubular probe with an internal volume of 1.1 μL is made of polypropylene hollow fiber with a supported liquid membrane of 85% nitrophenyloctyl ether (NPOE) with 15% bis(2-ethylhexyl)phosphonic acid (DEHP). The probe is connected on-line to the electrophoresis with short separation capillary via an air assisted flow gating interface cast from poly (dimethylsiloxane). The compact instrument is computer controlled via LabView. The probe parameters are tested for extraction of creatinine and basic amino acids from artificial solution and human urine. The sensitivity of the electrophoretic determination after 300 s extraction at 150 V compared to the sensitivity without extraction is 4.9-fold and 2.6-fold higher for creatinine and arginine, respectively. The RSDs for peak area measured from 5 repeated extractions of 50 μM solutions are 7.5%, 7.2%, 8.6% and 9.2% for Crea, Lys, Arg and His, respectively. The probe can be used for all-day measurements. The preparation of the probe is simple and requires no special tool.
