The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.
- MeSH
- 3D tisk * MeSH
- aplikace kožní MeSH
- imichimod * chemie aplikace a dávkování MeSH
- jehly * MeSH
- kožní absorpce MeSH
- kůže metabolismus MeSH
- mikroinjekce přístrojové vybavení MeSH
- nanočástice * chemie aplikace a dávkování MeSH
- polyethylenglykoly chemie aplikace a dávkování MeSH
- povidon chemie MeSH
- rozpustnost * MeSH
- systémy cílené aplikace léků přístrojové vybavení MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.
- MeSH
- akutní promyelocytární leukemie * diagnóza farmakoterapie epidemiologie MeSH
- dospělí MeSH
- incidence MeSH
- lidé MeSH
- patologická kompletní odpověď MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- sekundární malignity * farmakoterapie MeSH
- tretinoin MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
This study summarizes the response of cyanobacterium Spirulina subsalsa HKAR-19 under simulated light conditions of photosynthetically active radiation (PAR), PAR+UV-A (PA), and PAR+UV-A+UV-B (PAB). Exposure to UV radiation caused a significant (P < 0.05) decrease in chlorophyll a, phycocyanin, and total protein. In contrast, total carotene content increased significantly (P < 0.05) under PA and PAB with increasing irradiation time. The photosynthetic efficiency of photosystem II also decreased significantly in PA and PAB radiation. We have also recorded a decrease in the fluorescence emission intensity of phycocyanin under PA and PAB exposure. The phycocyanin fluorescence shifted towards shorter wavelengths (blue-shift) after 72 h of PA and PAB exposure. Intracellular reactive oxygen species (ROS) levels increased significantly in PA and PAB. Fluorescence microscopic images showed an increase in green fluorescence, indicating ROS generation in UV radiation. We have also quantified ROS generation using green and red fluorescence ratio represented as G/R ratio. A 2-6-fold increase in antioxidative enzymes activity was observed to overcome the damaging effects caused by UV stress as compared to untreated control cultures. The lipid peroxidation was assessed in terms of malondialdehyde content which increases significantly (P < 0.05) as the duration of exposure increases. These results suggest that a combined effect of PAR, UV-A, and UV-B was more deleterious than an individual one.
- MeSH
- antioxidancia * metabolismus MeSH
- chlorofyl a metabolismus MeSH
- chlorofyl * metabolismus MeSH
- fotosyntéza * účinky záření MeSH
- fotosystém II - proteinový komplex metabolismus MeSH
- fykokyanin * metabolismus MeSH
- karotenoidy metabolismus MeSH
- peroxidace lipidů účinky záření MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- Spirulina * účinky záření metabolismus MeSH
- ultrafialové záření * MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract. METHODS: Hard gelatin capsules and DRcapsTMcapsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms. RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcapsTM capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields. CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.
- MeSH
- bakteriální polysacharidy chemie MeSH
- biokompatibilní materiály chemie MeSH
- celulosa * chemie analogy a deriváty MeSH
- deriváty hypromelózy chemie MeSH
- hydrofobní a hydrofilní interakce * MeSH
- hydrogely chemie MeSH
- kofein chemie aplikace a dávkování MeSH
- kolon * metabolismus MeSH
- kyseliny polymethakrylové chemie MeSH
- léky s prodlouženým účinkem chemie MeSH
- polymery chemie MeSH
- polyvinyly chemie MeSH
- systémy cílené aplikace léků * metody MeSH
- tobolky * MeSH
- uvolňování léčiv * MeSH
- želatina * chemie MeSH
- železité sloučeniny chemie aplikace a dávkování MeSH
- Publikační typ
- časopisecké články MeSH
The current global scenario presents us with a growing increase in infections caused by fungi, referred to by specialists in the field as a "silent epidemic", aggravated by the limited pharmacological arsenal and increasing resistance to this therapy. For this reason, drug repositioning and therapeutic compound combinations are promising strategies to mitigate this serious problem. In this context, this study investigates the antifungal activity of the non-toxic, low-cost and widely available cationic polyelectrolyte Poly(diallyldimethylammonium chloride) (PDDA), in combination with different antifungal drugs: systemic (amphotericin B, AMB), topical (clioquinol, CLIO) and oral (nitroxoline, NTX). For each combination, different drug:PDDA ratios were tested and, through the broth microdilution technique, the minimum inhibitory concentration (MIC) of these drugs in the different ratios against clinically important Candida species strains was determined. Overall, PDDA combinations with the studied drugs demonstrated a significant increase in drug activity against most strains, reaching MIC reductions of up to 512 fold for the fluconazole resistant Candida krusei (Pichia kudriavzevii). In particular, the AMB-PDDA combination 1:99 was highly effective against AMB-resistant strains, demonstrating the excellent profile of PDDA as an adjuvant/association in novel antifungal formulations with outdated conventional drugs.
- MeSH
- amfotericin B farmakologie MeSH
- antifungální látky * farmakologie MeSH
- Candida * účinky léků MeSH
- fungální léková rezistence MeSH
- kandidóza mikrobiologie farmakoterapie MeSH
- kvartérní amoniové sloučeniny * farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- Pichia MeSH
- polyelektrolyty farmakologie MeSH
- polyethyleny farmakologie chemie MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- guselkumab,
- MeSH
- acitretin aplikace a dávkování MeSH
- biologická terapie metody MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * aplikace a dávkování MeSH
- lidé MeSH
- obezita komplikace MeSH
- psoriáza * farmakoterapie komplikace patologie MeSH
- terapie neúspěšná MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The aim of this study was to develop and validate methods for the determination of vitamins B2, B9, E and A in serum using liquid chromatography with mass spectrometry (MS) detection. Vitamin analysis was performed using an ultra performance liquid chromatography combined with tandem MS. The compounds were separated on a BEH C18 RP column (2.1 × 100 mm, 1.7 μm) using a gradient elution with an analysis time of 10 min. Sample preparation included protein precipitation with ethanol. The concentration range in human serum was as follows: riboflavin 5-1000 nmol/L, folic acid 2.5-250 nmol/L, α-tocopherol 0.5-100 μmol/L and all-trans-retinol 25-2500 nmol/L. Accuracy and precision were validated according to Food and Drug Administration guidelines, with coefficients of variation ranging from 3.1-11.7% and recoveries from 94.4-107.5%. Routine monitoring of the complex range of vitamins in bariatric medicine is still not common. This is despite the fact that patients are at risk for glitch deficits, especially of a neurological nature. An analytical method that allows for the complex measurement of both water-soluble and fat-soluble vitamins is important and necessary for the clinical monitoring of bariatric patients. The method we have described could benefit both clinical practice and nutritional research.
- MeSH
- alfa-tokoferol * krev MeSH
- bariatrická chirurgie MeSH
- chromatografie kapalinová metody MeSH
- kyselina listová * krev MeSH
- lidé MeSH
- limita detekce MeSH
- lineární modely MeSH
- reprodukovatelnost výsledků MeSH
- riboflavin * krev MeSH
- tandemová hmotnostní spektrometrie * metody MeSH
- vitamin A * krev MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Surgical site infection (SSI) is the most consistently reported complication of cranioplasty. No material showed a categorical superiority in the incidence of infection. Porous polyethylene (PE) is considered a low risk material regarding SSI. However, the literature data are very limited. Thus, our objective was to verify the assumed low incidence of SSI after PE cranioplasty in patients at high risk of SSI. The primary objective was the infection rate, while secondary objectives were implant exposure, revision and cosmetic results. METHOD: Patients who underwent three-dimensional (3D) personalized PE cranioplasty in the period 2014-2023 were evaluated prospectively. Only patients with an increased risk of SSI, and a satisfactory clinical conditions were included in the study. RESULTS: Thirty procedures were performed in 30 patients. Cranioplasty was performed 23 times after hemispheric decompressive craniectomy, five times after limited size craniotomy and two times after bifrontal decompressive craniectomy. Risk factors for the development of infection were 18 previous SSIs, 16 previous repeated revision surgeries, four intraoperatively opened frontal sinuses and two times radiotherapy. Neither infection nor implant exposure was detected in any patient. All patients were satisfied with the aesthetic result. In two cases, a revision was performed due to postoperative epidural hematoma. CONCLUSIONS: Three-dimensional personalized PE cranioplasty is associated with an extremely low incidence of SSI even in high-risk patients. However, our conclusions can only be confirmed in larger studies.
- MeSH
- dekompresní kraniektomie škodlivé účinky metody MeSH
- dospělí MeSH
- infekce chirurgické rány * epidemiologie etiologie MeSH
- kraniotomie škodlivé účinky metody MeSH
- lebka chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- polyethylen MeSH
- poréznost MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- zákroky plastické chirurgie * metody škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Background and Objectives: Surgical site infections (SSIs) are a significant complication following ventral hernia repair, potentially leading to prolonged hospital stays and increased morbidity. This study aimed to evaluate whether closed incision negative pressure wound therapy (ciNPWT) reduces the incidence of SSI after ventral hernia repair with polypropylene mesh compared to standard wound care. Materials and Methods: A randomized study was conducted with 100 patients undergoing ventral hernia repair using a polypropylene mesh. Participants were divided into two groups: a control group (n=50), which received standard sterile gauze dressing with an iodine-based disinfectant, and an intervention group (n=50), treated with the ciNPWT system (Vivano® by HARTMANN) for 5 days postoperatively. The primary outcome was the incidence of SSI within one year after surgery. Secondary outcomes included the influence of factors such as age, sex, smoking status, and hernia size on SSI occurrence. The study was approved by the Ethics Committee at the University Hospital Ostrava, adhering to the ethical standards of the Helsinki Declaration. Results: The incidence of SSI was lower in the ciNPWT group compared to the standard care group (4% vs. 12%), though this difference did not reach statistical significance. No significant effect of sex or smoking status on SSI was observed. The control group had a shorter mean length of hospital stay. Larger hernias in the non-ciNPWT group were more prone to SSIs, as expected. Conclusions: Although limited by a small sample size, the findings suggest that ciNPWT may be associated with a reduced rate of SSI following ventral hernia repair. Further studies with larger populations are needed to confirm these results.
- MeSH
- chirurgické síťky * MeSH
- dospělí MeSH
- incidence MeSH
- infekce chirurgické rány * prevence a kontrola epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- operace kýly * metody škodlivé účinky MeSH
- polypropyleny * MeSH
- senioři MeSH
- terapie ran pomocí řízeného podtlaku * metody MeSH
- ventrální hernie * chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
In this work, the solid-liquid equilibrium (SLE) curve for ten active pharmaceutical ingredients (APIs) with the polymer polyvinylpyrrolidone (PVP) K12 was purely predicted using the Conductor-like Screening Model for Real Solvents (COSMO-RS). In particular, two COSMO-RS-based strategies were followed (i.e., a traditional approach and an expedited approach), and their performances were compared. The veracity of the predicted SLE curves was assessed via a comparison with their respective SLE dataset that was obtained using the step-wise dissolution (S-WD) method. Overall, the COSMO-RS-based API-PVP K12 SLE curves were in satisfactory agreement with the S-WD-based data points. Of the twenty predicted SLE curves, only two were found to be in strong disagreement with the corresponding experimental values (both modeled using the expedited approach). Hence, it was recommended to use the traditional approach when predicting the API-polymer SLE curve. At the present moment, COSMO-RS may be an effective computational tool for the expeditious screening of API-polymer compatibility, particularly in the case of promising novel APIs, for which experimental datasets are likely limited or non-existent.
