Quorum Sensing allows bacteria to sense their population density via diffusible N-acyl homoserine lactone (N-HL) signaling molecules. Upon reaching a high enough cell density, bacteria will collectively exhibit a phenotype. Until recently, methods used for detection of N-HLs have not considered the chirality of these molecules and it was assumed that only the L-enantiomer was produced by bacteria. The production and effects of D-N-HLs have rarely been studied. In this work, the temporal production of D-N-HLs by the plant pathogen Pectobacterium atrosepticum and the human pathogen Pseudomonas aeruginosa are reported. Both bacteria produced D-N-HLs in significant amounts and in some cases their concentrations were higher than other low abundance L-N-HLs. Previously unreported D-enantiomers of N-3-oxoacyl and N-3-hydroxyacyl homoserine lactones were detected in P. atrosepticum. Interestingly, L-N-HLs produced in the lowest concentrations had relatively higher amounts of their corresponding D-enantiomers. Potential sources of D-N-HLs and their significance are considered.
The continuous expansion of research in the field of stable carboranes and their wide potential in the drug design require carrying out fundamental studies regarding their chiral separations. Although supercritical fluid chromatography (SFC) is a viable technique for fast enantioseparations, no investigation concerning boron cluster compounds has been done yet. We aimed at the development of a straightforward method enabling chiral separations of racemic mixtures of anionic cluster carboranes and metallacarboranes that represent an analytical challenge. The fast gradient screening testing nine polysaccharide-based columns was used. The key parameters affecting the selectivity were the type of chiral selector, the type of alcohol, and the base in cosolvent. Moreover, the addition of acetonitrile or water to the cosolvent was identified as an effective tool for decreasing the analysis time while preserving the resolution. After the optimization, the chiral separations of 19 out of 20 selected compounds were achieved in less than 10 min. These results demonstrate the clear advantage of SFC over chiral separations using HPLC in terms of both analysis time and structural variety of successfully separated compounds.
Boron cluster compounds are extensively studied due to their possible use in medicinal chemistry, mainly in the boron neutron capture anticancer therapy and as new innovative pharmacophores. Concerning this research, the chiral separations of exceptionally stable anionic 7,8-dicarba-nido-undecaborate(1-) and metal bis(dicarbollide(1-) derivatives with asymmetric substitutions remain the unsolved challenge of the chiral chromatography nowadays. Although the successful enantioseparation of some anionic 7,8-dicarba-nido-undecaborate(1-) ion derivatives were achieved in CZE with native β-cyclodextrins, it has not been observed with HPLC, yet. This study aimed to systematically investigate the enantioseparation of selected compounds in HPLC using native β-cyclodextrin and brominated β-cyclodextrin. The findings revealed positively charged strong adsorption sites on a stationary phase, identified as the cationic metal impurities in the silica-gel backbone. All the anionic species under the study were at least partially enantioseparated when a chelating agent blocked these cationic sites. Consequently, the first-ever HPLC enantioseparations of the 7,8-dicarba-nido-undecaborates(1-) were achieved. The brominated β-cyclodextrin seemed to be a better chiral selector for separation of these species, whereas the native β-cyclodextrin separated the anionic cobalt bis(dicarbollide(1-). The results of this study bring new information concerning the chiral separation of anionic boron clusters and might be used in the chiral method development process on other chiral selectors. Furthermore, the possibility of chiral separation of these species could influence the ongoing research areas of anionic boron clusters.
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing ʟ-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-ᴅ/ʟ-Pgl-Me, MIC < 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the ᴅ- and ʟ-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
- MeSH
- aminokyseliny chemie farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- antituberkulotika farmakologie MeSH
- Aspergillus flavus účinky léků MeSH
- buňky Hep G2 MeSH
- Candida albicans účinky léků MeSH
- chromatografie kapalinová MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium smegmatis účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- optická otáčivost MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- Pseudomonas aeruginosa účinky léků MeSH
- pyrazinamid chemie farmakologie MeSH
- Staphylococcus aureus účinky léků MeSH
- tuberkulóza farmakoterapie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Posturální instabilita a instabilita chůze patří mezi významné motorické symptomy Huntingtonovy nemoci (HN), které zvyšují riziko pádů. Rehabilitace je podstatnou součástí terapie instability. Cílem studie bylo zhodnotit, krátkodobý a dlouhodobý efekt multidisciplinárního rehabilitačního programu na posturální instabilitu i instabilitu chůze u HN a posoudit možnost provedení programu za hospitalizace. Metodika: 13 pacientů s HN bez těžšího kognitivního deficitu a deprese absolvovalo třítýdenní multidisciplinární rehabilitační program během hospitalizace, který byl specificky zaměřený na posturální stabilitu a stabilitu chůze. Vyšetření proběhla na začátku programu, po dokončení rehabilitace, po 1 a 3 měsících od dokončení. Testování zahrnovalo vyšetření stability chůze (Dynamic Gait Index; DGI), posturální stability pomocí posturografu na stabilní (PSS) and nestabilní 20% (PSU) plošině a motorické skóre pomocí Unified Huntington‘s Disease Rating Scale (UHDRS). Výsledky: PSS prokázalo statisticky významné zlepšení přetrvávající po dobu 3 měsíců a signifikantní zlepšení v DGI ihned po rehabilitaci. V motorickém skóre UHDRS a PSU statisticky významné zlepšení nalezeno nebylo. Závěr: Specifický rehabilitační program je bezpečný a dobře využitelný při terapii poruch stability u HN. Posturální stabilita dle PSS byla zlepšena po sledovanou dobu 3 měsíců. Zlepšení stability chůze dle DGI odeznělo do 1 měsíce. V PSU signifikantní zlepšení nebylo prokázáno. Tato studie nabízí návrh specifického rehabilitačního protokolu pro trénink stability u HN.
Aim: Postural and gait instability in Huntington‘s disease (HD) is a key component of the motor symptomatology which contributes to an increased risk of falls. Rehabilitation is considered beneficial in postural and gait stability treatment. We aimed to explore the feasibility and the short- and long-term effects of an inpatient multidisciplinary rehabilitation program on postural and gait stability in subjects with HD. Methods: A sample of 13 subjects with HD but with no severe cognitive deficit or depression underwent a 3-week specific inpatient rehabilitation program focused on postural and gait stability. Patients were examined at the baseline, after the completion of rehabilitation, and then 1 month and 3 months after the end of the program. The testing included: gait stability examination (Dynamic Gait Index; DGI), posturography examination of postural stability on a stable (PSS) and 20% unstable (PSU) platform and the total motor score evaluation by Unified Huntington‘s Disease Rating Scale (UHDRS). Results: There was a significant improvement lasting 3 months in PSS and a significant improvement in DGI immediately after the rehabilitation. There was no significant improvement in the PSU and UHDRS total motor score. Conclusion: Specific rehabilitation methods are safe and feasible and may be beneficial in the treatment of postural and gait instability in patients with early and mid-stage HD. The postural instability improvement measured by PSS persisted for at least 3 months. The gait stability improvement in DGI did not persist after 1 month. We found no improvement in PSU. This exploratory study offers a sample of a specific rehabilitation protocol for stability training in HD.
- Klíčová slova
- instabilita,
- MeSH
- chůze MeSH
- dospělí MeSH
- Huntingtonova nemoc * komplikace rehabilitace MeSH
- klinická studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- rehabilitace metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Objective: The safety of comfrey herbal cream application to broken skin is still a matter of regulatory debate. It was therefore examined in children with intact and with broken skin treated for blunt traumas and sports injuries, with the aim of collecting data for pharmacovigilance and clinical safety assessments. Methods: A total of 712 children (386 children with intact skin and 326 children with abrasions and superficial wounds) were openly treated for up to 2 weeks with 1-5 applications daily of comfrey herb cream after presenting for blunt traumas and sports accidents. The incidence rate of adverse events was calculated, next to a global assessment of treatment effects. Results: No adverse events occurred in the group of children with intact skin, and one intolerability reaction (burning and reddening) was observed after application to broken skin. The overall incidence rate of intolerability reactions per patient was calculated as 0.14% (95% CI 0.00-0.78%) and that of systemic adverse effects as 0.00% (95% CI 0.00-0.42%). Accordingly, the probability of the occurrence of local reactions and systemic adverse events is well below, which is one in 100 treated patients. The global assessment of effects corresponded to previously published experience. Conclusion: These studies confirm an excellent benefit-to-risk ratio for the application of comfrey herb cream in the treatment of blunt traumas and sports injuries in children with intact and with broken skin.
- Publikační typ
- časopisecké články MeSH
Charcot-Marie-Tooth je geneticky podmíněná periferní neuropatie s rozvojem svalových dysbalancí a kontraktur svalů a vazivových struktur. S věkem dochází též k rozvoji deformit kostí a kloubů nohy a ruky. Průběh onemocnění je variabilní, klinický nález kolísá i v rámci jedné rodiny od asymptomatických až po těžce postižené jedince. Diagnostika je neurologická (elektrodiagnostika), molekulárněgenetická (analýza DNA) a klinická. Kauzální terapie CMT choroby neexistuje. Symptomatická léčba zahrnuje terapii medikamentózní, rehabilitační, protetickou a operační v závislosti na tíži a prognóze postižení a subjektivních potížích pacienta. Ortopedická operační léčba CMT se na našem pracovišti týká převážně oblasti nohy. Na základě dominujícího patologického obrazu provádíme kombinované operační výkony na měkkých tkáních, skeletu a kloubech. Taktika léčby vychází z individuality a potřeb pacienta a prognózy postižení. Pro strategii je charakteristická kombinace operací od jednodušších (měkké tkáně, jednoduché osteotomie) po složitější (artrodézy), tzv. krok za krokem, se snahou o maximální korekci deformity v jednom operačním sezení.
Charcot-Marie-Tooth disease is a genetically determined polyneuropathy presenting with muscle imbalance and contractures. It is often associated with bone and joint deformities of the feet and hands. The progress of the disease is very individual and clinical pictures can vary even within a single family, with some CMT individuals being almost asymptomatic while others being quite severely affected. CMT diagnosis is based on electromyographic studies and DNA analysis. Curative therapy is unknown. Symptomatic therapy involves medication, rehabilitation, prosthetic care and orthopaedic surgical procedures depending on actual clinical picture, subjective symptoms and progression. Orthopaedic surgical treatment mostly concerns feet deformities. Depending on clinical picture and imaging studies, soft tissue, bone and/or joint procedures can be done. Surgical treatment approach must be strictly individual based on expected progression of the disease. Our surgical treatment approach is to start with easier procedures done on soft tissues or simple osteotomies, later more complicated joint procedures and finally arthrodesis is often indicated. It is advisable to proceed step by step aiming for maximum bone and joint deformity correction within one surgical procedure.
