Nowadays, most of the newly developed active pharmaceutical ingredients (APIs) consist of cohesive particles with a mean particle size of <100μm, a wide particle size distribution (PSD) and a tendency to agglomerate, therefore they are difficult to handle in continuous manufacturing (CM) lines. The current paper focuses on the impact of various glidants on the bulk properties of difficult-to-handle APIs. Three challenging powders were included: two extremely cohesive APIs (acetaminophen micronized (APAPμ) and metoprolol tartrate (MPT)) which previously have shown processing issues during different stages of the continuous direct compression (CDC)-line and a spray dried placebo (SD) powder containing hydroxypropylmethyl cellulose (HPMC), known for its sub-optimal flow with a high specific surface area (SSA) and low density. Four flow-enhancing excipients were used: a hydrophilic (Aerosil® 200) and hydrophobic (Aerosil® R972) fumed silica grade, a mesoporous silica grade (Syloid® 244FP), and a calcium phosphate excipient (TRI-CAFOS® 200-7). The APIs and binary API/glidant blends (varied between 0.5-2.75 w/w%) were characterized for their bulk properties relevant for CDC. The results indicated that optimizing different bulk parameters (e.g., density, flow, compressibility..) of an API required varying weight percentages of the glidant (e.g., different surface area coverage (SAC)) depending on the APIs. Moreover, even at similar SAC, the impact of the glidant on the bulk characteristic of the APIs depended on the glidant type properties. While nano-sized silicon dioxide were effective for improving the flowability of a powder, other glidants (mesoporous silica and tricalcium phosphate (TCP)) showed also promise as alternatives. Additionally, an excess of glidant, referred to as oversilication, negatively impacted some bulk parameters, but other characteristics were unaffected. Finally, to determine the appropriate concentration of the different classes of glidants, SAC calculations, an understanding of the glidant's working mechanism, and knowledge about the API's characteristics (i.e., morphology, compressibility, flowability, aeration, density, and wall friction) are required. This study confirmed the necessity of including various material characterization techniques to assess the impact of glidants on the bulk characteristics of APIs.
- MeSH
- deriváty hypromelózy * chemie MeSH
- farmaceutická chemie metody MeSH
- fosforečnany vápenaté * chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- metoprolol * chemie MeSH
- nerozplněné léky MeSH
- oxid křemičitý chemie MeSH
- paracetamol * chemie MeSH
- pomocné látky * chemie MeSH
- prášky, zásypy, pudry * MeSH
- příprava léků metody MeSH
- reologie * MeSH
- velikost částic * MeSH
- Publikační typ
- časopisecké články MeSH
It was to investigate the clinical efficacy of the combination therapy of fluticasone propionate inhalation aerosol and vitamin D (VD) in pediatric bronchial asthma (BA) and analyze the correlation between serum 25-(OH)-D3 levels and immune function, as well as calcium-phosphorus metabolism. A total of 110 patients with BA were recruited. Regarding treatment plan, patients were randomly rolled into a single-drug treatment group (SDT, treated with fluticasone propionate inhalation aerosol alone) and a dual-drug treatment group (TDT, treated with the combination of fluticasone propionate inhalation aerosol and VD). The changes in serum 25-(OH)-D3 levels, immunoglobulins, T lymphocyte subsets, and inflammatory cytokine levels in children with BA under different treatment modalities were compared. Clinical symptom disappearance, asthma control, and quality of life (QoL) were assessed, and the total effective rate and adverse reactions (ARs) were compared. A control group consisting of 60 healthy children who underwent concurrent physical examinations was included. The differences in serum 25-(OH)-D3 levels, immunoglobulins, and T lymphocyte subset levels between children with BA and healthy controls were compared, and their correlations were analyzed. The TDT group showed a drastic reduction in the disappearance time of lung wheezing and dyspnea relative to the SDT group. Furthermore, the TDT group exhibited notable improvements in lung function parameters, including forced vital capacity (FVC), forced expiratory volume at one second (FEV1), FEV1/FVC, and peak expiratory flow (PEF). Blood gas analysis revealed a great decrease in PaCO2 and an increase in PaO2. The Childhood Asthma Control Test (C-ACT) scores for asthma control and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores for QoL showed marked increases in the TDT group. Moreover, the TDT group demonstrated notable increases in serum 25-(OH)-D3 levels, immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets (CD4+ and CD8+), as well as blood calcium and phosphorus levels. Additionally, the TDT group exhibited a prominent increase in the anti-inflammatory cytokine interleukin (IL)-10 level and a drastic decrease in the pro-inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-alpha) levels (all P<0.05). The total effective rates of treatment in the SDT group and TDT group were 83.64 % and 96.36 %, respectively, with AR rates of 16.36 % and 7.27 %. The TDT group exhibited a superior total effective rate and an inferior incidence of ARs to the SDT group (both P<0.05). Additionally, in contrast to the control group, the BA group showed notable decreases in serum 25-(OH)-D3 levels, immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets (CD4+, CD8+, and CD4+/CD8+), as well as blood calcium and phosphorus levels (all P<0.05). Prior to treatment, there was a positive correlation between serum 25-(OH)-D3 levels and immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets (CD4+ and CD8+), as well as blood calcium and phosphorus levels in children with BA (P<0.05). In patients with BA, combined treatment with inhaled fluticasone propionate aerosol and VD may have a regulatory effect on serum 25-hydroxyVD levels, immune function, and calcium-phosphate metabolism. The correlation between serum 25-(OH)-D3 levels and immune function, as well as calcium-phosphate metabolism, suggested that VD may play a crucial role in the immune regulation and calcium-phosphate metabolism of BA.
- MeSH
- aplikace inhalační MeSH
- bronchiální astma * farmakoterapie krev imunologie MeSH
- bronchodilatancia aplikace a dávkování terapeutické užití MeSH
- dítě MeSH
- flutikason aplikace a dávkování terapeutické užití MeSH
- fosfáty krev MeSH
- kombinovaná farmakoterapie * MeSH
- kvalita života MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- vápník krev MeSH
- vitamin D * krev analogy a deriváty terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Biofilm formation is an effective survival strategy of plant-associated microorganisms in hostile environments, so the application of biofilm-forming and exopolysaccharide (EPS)-producing beneficial microbes to plants has received more attention in recent years. This study examined the ability of biofilm and EPS production of Bacillus subtilis and Bacillus thuringiensis strains under different NaCl concentrations (0, 50, 100, 200, and 400 mmol/L), pH values (5.5, 6.5, 7.5, and 8.5), and phosphate levels (0, 25, 50, and 100 mmol/L at 0 and 400 mmol/L NaCl). B. subtilis BS2 and B. thuringiensis BS6/BS7 strains significantly increased biofilm formation in a similar pattern to EPS production under salt stress. B. subtilis BS2/BS3 enhanced biofilm production at slightly acidic pH with a lower EPS production but the other strains formed considerably more amount of biofilm and EPS at alkaline pH. Interestingly, higher levels of phosphate substantially decreased biofilm and EPS production at 0 mmol/L NaCl but increased biofilm formation at 400 mmol/L salt concentration. Overall, contrary to phosphate, salt and pH differently influenced biofilm and EPS production by Bacillus strains. EPS production contributed to biofilm formation to some extent under all the conditions tested. Some Bacillus strains produced more abundant biofilm under salt and pH stress, indicating their potential to form in vivo biofilms in rhizosphere and on plants, particularly under unfavorable conditions.
- MeSH
- Bacillus subtilis fyziologie metabolismus účinky léků MeSH
- Bacillus thuringiensis fyziologie účinky léků MeSH
- bakteriální polysacharidy * metabolismus biosyntéza MeSH
- biofilmy * účinky léků růst a vývoj MeSH
- chlorid sodný * farmakologie metabolismus MeSH
- fosfáty * metabolismus farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- Publikační typ
- časopisecké články MeSH
Autoři v článku prezentují epidemiologii, rizikové faktory přispívající ke vzniku urolitiáz, věnují se dále laboratornímu vyšetření u litiatiků, včetně problematiky analýzy složení konkrementů a jeho významu. Hlavním cílem článku je předložení metod neinvazivní léčby jednotlivých typů litiázy, především metafylaxe u pacientů s litiázou, a to jak režimových opatřeních, tak i užití farmak, které přispívají ke snížení četností recidiv litiázy, ale i komplikacím, které jsou s tímto onemocněním spojené.
The authors present the epidemiology, risk factors contributing to the development of urolithiasis, laboratory examination in lithiatic patients, including the analysis of the composition of concrements and its significance. The main goal of the article is to present the methods of non-invasive treatment of different types of lithiasis, especially metaphylaxis in patients with lithiasis, both regimen measures and the use of drugs that contribute to reducing the frequency of recurrences of lithiasis, as well as complications associated with this disease
- MeSH
- alopurinol farmakologie terapeutické užití MeSH
- analýza moči metody MeSH
- cystinurie farmakoterapie komplikace MeSH
- difrakce rentgenového záření metody MeSH
- diuretika farmakologie terapeutické užití MeSH
- hydroxyapatit terapeutické užití MeSH
- hyperkalciurie farmakoterapie komplikace MeSH
- hyperoxalurie farmakoterapie komplikace MeSH
- hyperurikemie farmakoterapie komplikace MeSH
- infekce močového ústrojí etiologie komplikace MeSH
- kaliumcitrát farmakologie terapeutické užití MeSH
- kaménky etiologie klasifikace terapie MeSH
- klinické laboratorní techniky metody MeSH
- lidé MeSH
- oxaláty škodlivé účinky MeSH
- rizikové faktory MeSH
- urolitiáza * diagnóza farmakoterapie prevence a kontrola MeSH
- vápník dietní terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Obor medicinální chemie se často potýká s problémem suboptimálních vlastností aktivních látek. Za účelem zlepšení těchto vlastností byla vyvinuta řada důmyslných přístupů tvorby proléčiv. Proléčivo je inaktivovaná forma léčiva, která dočasně modifikuje jeho vlastnosti. V těle je pak proléčivo (nejčastěji enzymaticky) transformováno zpět na aktivní léčivo. Proléčiva mohou upravit řadu vlastností jako např. absorpci, rozpustnost, či cílené doručení do tkáně. Poměr proléčiv mezi schválenými léky v posledních letech stoupá, což podtrhuje význam této strategie pro medicinální chemii i klinické využití.
The field of medicinal chemistry is often struggling with suboptimal properties of active compounds. To address this issue, many sophisticated prodrug approaches have been developed. Prodrug is an inactive form of a drug which temporarily alters its properties. In the body, the prodrug is (most often enzymatically) transformed back to the parent active drug. Prodrugs can modify variety of properties such as absorption, solubility, or tissue targeted delivery. The number of prodrugs among approved drugs has been rising in the past years which underlines the importance of prodrugs for medicinal chemistry and clinical use.
Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.
- MeSH
- fosfáty * chemie MeSH
- histidin * chemie MeSH
- koncentrace vodíkových iontů MeSH
- kyselina citronová chemie MeSH
- lyofilizace * metody MeSH
- magnetická rezonanční spektroskopie * metody MeSH
- pufry MeSH
- spektrofotometrie ultrafialová metody MeSH
- trehalosa * chemie MeSH
- Publikační typ
- časopisecké články MeSH
Phosphate-solubilising fungi (PSF) are beneficial microorganisms that play a pivotal role in plant growth by increasing the availability of phosphorus (P) in soil. Although phosphorus is an essential nutrient for plants, it often becomes inaccessible as it binds into insoluble forms. PSF effectively facilitate the release of this bound phosphorus through diverse mechanisms. Numerous fungal species demonstrate the ability to solubilise various types of phosphate compounds. Among the commonly researched PSF are Penicillium, Aspergillus, Rhizopus, Fusarium, Trichoderma, and Sclerotium. Moreover, yeasts such as Saccharomyces cerevisiae can potentially be leveraged as PSF. PSF secrete organic acids that chelate phosphate ions, thereby increasing their solubility in the soil. Moreover, PSF contribute to the decomposition of organic phosphorus compounds in soil by employing enzymes such as phosphatases, phytases, and phosphonatases. Furthermore, PSF can interact with other soil microorganisms, including nitrogen-fixing bacteria and arbuscular mycorrhizal fungi (AM-fungi), fostering synergistic effects that further enhance plant growth and nutrient absorption. The utilisation of PSF as biofertilisers offers numerous advantages over chemical fertilisers, including environmental friendliness, cost-effectiveness, and enhanced fertiliser utilisation efficiency. Furthermore, PSF can prove beneficial in challenging environments characterised by high phosphate sorption. Hence, this review serves as an updated study aimed at broadening the understanding of PSF and its potential applications in P solubilisation. This review also focuses on the diversity of PSF, the mechanisms underlying solubilisation, ecological roles of PSF in soil microbiome, and the benefits of sustainable agriculture. By delving into the ecological roles of PSF and their potential as biofertilisers, this study contributes to a deeper understanding of sustainable agriculture practices and addresses challenges in phosphate-scarce environments.
- MeSH
- fosfáty * metabolismus MeSH
- fosfor metabolismus MeSH
- houby * metabolismus růst a vývoj MeSH
- mykorhiza metabolismus fyziologie MeSH
- průmyslová hnojiva * analýza MeSH
- půda chemie MeSH
- půdní mikrobiologie * MeSH
- vývoj rostlin * MeSH
- zemědělství * metody MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria.
- MeSH
- elektronová kryomikroskopie MeSH
- fosforylace MeSH
- lidé MeSH
- mitochondrie * metabolismus MeSH
- polyfosfáty * metabolismus MeSH
- proteasa La * metabolismus MeSH
- proteinové domény MeSH
- tyrosin * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
220 stran : ilustrace (některé barevné) ; 24 cm
Publikácia, ktorá sa zameriava na biokompatibilné kostné cementy vyrobené z fosforečnanu vápenatého a používané v liečbe defektov kostí a chrupavky. Určené odbornej verejnosti.
- MeSH
- biokompatibilní materiály MeSH
- fosforečnany vápenaté MeSH
- kostní cementy MeSH
- nemoci chrupavky MeSH
- nemoci kostí MeSH
- regenerace kostí MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- biomedicínské inženýrství
- technika lékařská, zdravotnický materiál a protetika
- ortopedie
- NLK Publikační typ
- kolektivní monografie
